A 56 year old woman presents to the emergency department with several days history of diarrhoea. She is a little confused and unsteady on her feet. Her past medical history includes hypertension and manic depressive disorder and she is well otherwise. She is on Lithium and an antihypertensive.
She denies trauma, or headache, or visual disturbance.
Her vitals are pulse rate of 93bpm, respiratory rate of 16 , BP of 135/80 and physical examination reveals dual heart sounds, normal air entry bilaterally and soft, lax abdomen. Her motor and sensory neurological exam shows PERLA, upper and lower limbs are essentially normal, and there are no cerebellar signs. When gait is tested, there is no broad based gait, but she is unsteady on her feet and cannot perform heel to toe.
Differentials Please:
I must admit, I only had a couple of differentials for this patient:
1 Intra-cranial pathology- space occupying lesion in the cerebellum, or a bleed(but strange not to have a headache)
2 Lithium Toxicity
Investigations included basic bloods and ECG and Lithium levels.
Blood tests revealed:
Normal Na, K but Urea of 6.8 and creatinine of 126(50-90)
The lithium level is 2.7(critical high is >2)
ECG is normal.
The most likely diagnosis in this patient is lithium toxicity secondary to dehydration from her diarrhoea….. Or is the diarrhoea a symptom of her Lithium toxicity?
Lithium is used for bipolar and affective disorder. It competes with sodium and potassium, displacing them from intracellular sites. It is metabolised almost exclusively in the kidney, with a small amount (~5%) eliminated is sweat/saliva. Lithium concentration depends on the glomerular filtration rate. It has a low therapeutic index ie., a narrow range between therapy and toxicity.
A little bit more on pharmacology:
Peak absorption occurs in 1 to 4 hours, with complete absorption in 8 hours. Its half life is about 24 hours and is excreted unchanged.
Excretion is primarily renal and occurs in two phases.
-2/3 of single dose is cleared in the urine by 6 to 12 h.
- the remainder is completely cleared over 10 to 14 days.
Lithium has complete glomerular filtration;
-The proximal convoluted tubule reabsorbs 60 to 80%.
-There is no absorption in the distal tubule.
50% is eliminated within 6-12 hours, and 50% in 10-14 days via slow excretory phase.
Both therapeutic action and toxic effects of lithium are mediated intracellularly. Thus lithium serum levels may not be a true reflection of the biologically active tissue portion.
ANYTHING THAT AFFECTS WATER AND ELECTROLYTE BALANCE CAN LEAD TO LITHIUM TOXICITY.
Clinical Presentations
Generally patients present with altered mental status, tremor and cerebellar dysfunction. As the level of toxicity increases, this can include extrapyramidal signs.
Up to 12% develop nephrogenic diabetes insipidus.
Overdose can be acute, chronic, or acute –on-chronic. Acute overdoses are tolerated more than chronic toxicity and present with more gastrointestinal complaints, including nausea, vomiting and diarrhoea, than CNS effects
Electrocardiographic abnormalities can occur and they are related to intracellular hypokalaemia, due to Lithium interfering with Na-K channels. The ECG changes include:
1 U waves
2 Flattened/inverted T waves
3 ST depression
Although the diabetes insipidus and conduction abnormalities will resolve, some of the neurological effects such as cerebellar dysfunction, can be permanent.
TREATMENT
Manage the patient appropriately including stabilisation of blood pressure
Treat seizures with benzodiazepines
CHARCOAL DOES NOT WORK. The only indication for charcoal is suspected multiple drug overdose.
Whole bowel irrigation is sometimes used, but must be sorted early.
Normal Saline is VERY IMPORTANT. Most patients will have some fluid or sodium deficit. Replacement of fluid loss improves renal elimination of lithium.
FORCED DIURESIS with diuretics is of no use and may result in further Na and fluid losses.
Haemodialysis is indicated in severely toxic patients. Although there is a significant lack of agreement in the literature about specific indications for haemodialysis, the guidelines commonly include:
-altered mental status
-impaired renal functionm
-lithium levels >4mEq/L in acute toxicity and 2mEq/L in chronic.
Haemodialysis removes serum lithium, reducing CNS levels of lithium. This theoretically should reduce the risk of permanent neurological sequelae, although there is no evidence for this.
SUPPORTIVE CARE/DISPOSITION
The patient will need electrolyte and renal function monitored, as well as fluid balance. In conduction abnormalities, cardiac monitoring is advised and in the more severe intoxications, ICU/HDU admissions.
This patient was treated with normal saline, lithium was ceased and was admitted under a toxicologist.
Dr Clifford Tan, Emergency Physician and Toxicologist, on our resus.com.au faculty, admitted and managed this patient.
Dr Tan any comments, insights, corrections? Also, what was the patient’s progress like?
