Lithium: Anesthetic interactions

Lithium is a commonly used mood stabilizing drug. One of lithium’s proposed mechanisms of action is a reduction in the release of neurotransmitters in the central nervous system (CNS) and peripheral nervous system (PNS) which also may lead to many of its adverse side effects and anesthetic interactions. Unfortunately, despite its clinical benefit, lithium has a narrow therapeutic ratio. It has numerous side effects including interference of antidiuretic hormone (ADH) action, cardiac dysrhythmias, gastrointestinal disturbances, and tremor. Because lithium is excreted solely by the kidney, patients with renal failure are at increased risk for adverse effects and anesthetic interactions.

Lithium binds voltage-gated sodium channels and result in a decrease duration of action potential. It binds and detaches from the sodium channel rapidly and have a greater affinity for the active and inactivated (but not rising) state. It reduces excitatory neurotransmission while increasing GABA or inhibitory neurotransmission.

Anesthetic interactions include:

• Prolongation of depolarizing neuromuscular block (DNMB): Lithium prolongs the latency (time to onset) and the duration of neuromuscular blockade produced by both depolarizing and nondepolarizing NMBs. The mechanism is thought to be due to lithium-induced inhibition of synthesis and release of acetylcholine at neuromuscular junction as well as competition with sodium ions during depolarization event. It decreases acetylcholine release from alpha motor neurons at the neuromuscular junction. It also activates potassium channels and this inhibits neuromuscular transmission presynaptically and muscular contraction postsynaptically. The combination of lithium and nondepolarizing blockers results in a synergistic inhibition of neuromuscular transmission. The combination of lithium and succinylcholine results in additive inhibition.

• Reduction in the requirements of anesthetic agents blocks brainstem release of norepinephrine, epinephrine, and dopamine.

• Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the excretion of lithium by the kidneys, and it can result in toxic plasma levels.

• Toxic symptoms tend to occur with plasma levels of >1.5 mmol litre−1. Thus, it is generally advised that lithium should be stopped at least 24 hours before surgery.