Lithium and sinus node dysfunction

Lithium and sinus node disease

Lithium is used in the treatment of bipolar disorder. It has a narrow therapeutic index (range between the therapeutic dose and the toxic dose). Lithium can cause bradycardia directly by its effect on the sinus node or indirectly through induction of hypothyroidism. Sometimes the bradycardia may be severe enough to require temporary pacing. Usually the bradycardia improves once the lithium levels come down. Thyroid status also improves after withdrawal of lithium. It must be remembered that diuretics can aggravate lithium toxicity as lithium is selectively reabsorbed by the renal tubules. This can also occur in association with sodium deficiency or dehydration secondary to vomiting or diarrhoea. Renal disease can also precipitate lithium toxicity.

There is also a case report of irreversible sinus node dysfunction occurring after restarting lithium. The person had initially developed sinus dose dysfunction with long term lithium therapy, which improved on discontinuing lithium. But after resuming low dose of lithium, irreversible sinus node dysfunction occurred (not improving by stopping lithium again) and a permanent pacemaker had to be implanted [1]. This report gives a suggestion that it may better not to re-challenge with lithium once the sinus node dysfunction improves after withdrawal of the drug. It may be prudent to consider an alternate medication.

Lithium is a potent blocker of cardiac sodium channel which could have a role in lithium induced bradycardia. Sinus arrest while it was being used in therapeutic dose, requiring permanent pacemaker has been reported [2]. Lithium therapy was continued in this case after insertion of rate modulated ventricular pacemaker.

Lithium induced sinus node dysfunction can also occur within therapeutic levels of lithium as mentioned above. Therapeutic levels of lithium are in the range of 0.6–1.2 mEq/l. In another case sinus node arrest and intermittent junctional escape occurred at serum lithium level of 0.7 mmol/L [3]. The patient was supported with temporary pacing and the condition improved after withdrawal of lithium. Serum electrolytes and thyroid function were normal in this case. In another similar report, symptomatic sinus bradycardia occurred at serum lithium level of 0.55 mmol/L [4]. That patient improved after lithium withdrawal and did not need pacemaker support.

References

1. Terao T, Abe H, Abe K. Irreversible sinus node dysfunction induced by resumption of lithium therapy. Acta Psychiatr Scand. 1996;93:407-8.
2. Gavin Y Oudit, Victoria Korley, Peter H Backx, Paul Dorian. Lithium-induced sinus node disease at therapeutic concentrations: linking lithium-induced blockade of sodium channels to impaired pacemaker activity. Can J Cardiol. 2007 Mar 1;23(3):229-32.
3. Shetty RK, Vivek G, Parida A, Chetty S. Lithium-induced sinus node dysfunction at therapeutic levels. BMJ Case Rep. 2013 Jan 22;2013:bcr2012008107.
4. Ataallah B, Al-Zakhari R, Sharma A, Tofano M, Haggerty G. A Rare but Reversible Cause of Lithium-Induced Bradycardia. Cureus. 2020 Jun 13;12(6):e8600.