Lithium


  Issues for Surgery


Exacerbation of symptoms of mania, bipolar disorder or recurrent depression if omitted.

Potential toxicity secondary to dehydration if continued (see Further Information).


  Advice in the Perioperative period


Elective Surgery

Check urea and electrolytes (U&E’s), thyroid function and ECG pre-operatively unless recently checked (see Further Information).

Minor Surgery
Continue1.

Major Surgery
Stop 24 hours before operation1, 2, 3.

Emergency Surgery

If there is insufficient time to follow the advice for elective surgery, ensure adequate hydration and monitor renal function closely.

Post-operative Advice

Restart post-operatively when next dose due providing renal function stable.

Monitor electrolytes closely and ensure adequate hydration.


  Interaction(s) with Common Anaesthetic Agents


Neuromuscular blocking drugs (NMBDs)

Lithium possibly prolongs the effects of both depolarizing and non-depolarizing NMBDs1, 2, 4, 5. Four case reports note potentiation of the effect of standard doses of pancuronium when administered alone or in combination with suxamethonium. The mechanism for this is not known although it has been suggested to be due to lithium induced changes in electrolyte balance causing release of acetylcholine. Other case reports indicate no instances of unusually prolonged recovery from suxamethonium in patients taking lithium4.

Concurrent use of lithium and NMBDs need not be avoided but appropriate neuromuscular monitoring should be performed intraoperatively2, 4.

Barbiturates

Case reports have described a prolonged hypnotic effect in barbiturate-based anaesthesia (e.g. thiopental) in patients who are taking lithium, although in one report the plasma lithium level was above the normal therapeutic range2.

Reduced anaesthetic requirements

Lithium may decrease anaesthetic requirements because it blocks brainstem release of noradrenaline / norepinephrine, adrenaline / epinephrine and dopamine3, 5, 6.

Central Nervous System (CNS) Excitation (Serotonin Syndrome)

Some opioids act as weak serotonin reuptake inhibitors (SRIs) and can precipitate serotonin syndrome in conjunction with other serotonergic medication. Symptoms of serotonin syndrome may occur if lithium is given concomitantly with1, 4: -

  • fentanyl
  • methadone
  • pentazocine
  • pethidine
  • tapentadol
  • tramadol

Patients should be monitored closely and the possibility of serotonin toxicity considered if patients experience altered mental state, autonomic dysfunction or neuromuscular adverse effects with concomitant treatment1.

Seizure threshold

Lithium can lower the seizure threshold; concurrent use with other medications that lower the seizure threshold (e.g. anaesthetic agents, tramadol) may have an additive effect on the risk of seizure1, 7.


  Interaction(s) with other Common Medicines used in the Perioperative Period


CNS Excitation (Serotonin syndrome)

Opioids
For a discussion of opioids see under Interaction(s) with Common Anaesthetic Agents above.

Methylthioninium chloride (methylene blue)
The MHRA advise that methylthioninium chloride should be avoided in patients taking drugs that enhance serotonergic transmission (e.g. lithium). If concurrent use is necessary the lowest possible dose of methylthioninium chloride should be given and the patients should be closely monitored for signs of CNS toxicity for 4 hours after administration. However, this advice is contested in one report which suggests even doses as low as 1mg/kg may be sufficient to inhibit monoamine oxidase-A, thus causing a reaction4.

Other Medications
There is also an increased risk of developing serotonin syndrome when lithium is used concurrently with the following1, 4: -

  • granisetron
  • linezolid
  • ondansetron

Monitor patients for symptoms of serotonin syndrome such as fever, tremors, diarrhoea, and agitation. Concurrent treatment should be stopped if serotonin syndrome occurs1.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs)

Lithium has a narrow therapeutic index; this means there is a narrow margin between serum concentrations that are therapeutic and those that are toxic. NSAIDs increase lithium levels; the manufacturers advise monitoring serum lithium concentrations if initiating NSAIDs7. Ideally perioperative use of NSAIDS should be avoided3.

Seizure Threshold (see Interaction(s) with Common Anaesthetic Agents above).


  Further Information


Pre-operative Monitoring

Long-term treatment with lithium can cause hypothyroidism, renal impairment and cardiac disorders so the manufacturers advise regular monitoring of thyroid, renal and cardiac function7. It is advisable to check urea and electrolytes (U&E’s), thyroid function and ECG preoperatively unless recently checked.

If lithium toxicity is suspected (symptoms include nausea, diarrhoea, blurred vision, polyuria, light headedness, fine resting tremor, muscular weakness and drowsiness7) consider checking trough serum lithium level.

Hydration

Dehydration and hyponatraemia should be avoided as toxicity can occur7.


  References


  1. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com  [Accessed on 13th May 2019]
  2. Flood, S. & Bodenham, A. Lithium: mimicry, mania, and muscle relaxants. Continuing Education in Anaesthesia Critical Care & Pain. 2010;10(3):77-80
  3. Peck, T. Wong, A. & Norman, E. Anaesthetic implications of psychoactive drugs. Continuing Education in Anaesthesia Critical Care & Pain. 2010;10(6):177-181
  4. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com  [Accessed on 13th May 2019]
  5. Kaye, A. Kline, R. Thompson, E. et. al. Perioperative implications of common and newer psychotropic medications used in clinical practice. Best Practice & Research: Clinical Anaesthesiology. 2018;32(2):187-202
  6. Fleisher, L. & Mythen, M. (2015). Anesthetic Implications of Concurrent Diseases. Chapter in Miller’s Anesthesia, 8th Edition. Elsevier Saunders
  7. Summary of Product Characteristics – Priadel ® (lithium). Sanofi. Accessed via www.medicines.org.uk   13/05/2019 [date of revision of the text September 2018]