Albany Medical Review - August 2001

Case Report -
A 51-year-old male found in a confused state

Rommel M. Tolentino, MD

A 51-year-old Caucasian male was brought to the ER by police after found wandering in a local park in a confused state. The patient told the police he was attempting to walk a distance of 30 miles away to visit his ex-wife. The patient admitted to a history of marijuana use but denied any alcohol or other illicit drug use at this time. His past medical history was significant for bipolar disorder as well as polysubstance abuse (alcohol and cannabis). There was no significant family history. The patient was divorced and had two teen-aged daughters. He had no allergies. His current medications included Lithium SA 450 mg BID, Perphenazine 24 mg qhs, and Clonazepam 5 mg qhs.

Review of systems at the time of initial assessment was positive only for a cough and a tremor of both hands. Vital signs were within normal limits. He was alert and oriented to time, place, and person. Head and neck exam revealed no abnormalities, pupils were equal and reactive and no nystagmus was noted. Heart exam was normal and lungs were clear to auscultation bilaterally. Abdominal exam was benign. Mental status exam revealed psychomotor retardation, and loosening of associations with respect to speech content, although his concentration ability was intact. The patient appeared ataxic and had an intention tremor in both hands.

A complete metabolic profile showed a mild hyponatremia (Na 133), and a slightly elevated SGOT of 53. A CBC showed an elevated white blood cell count of 15.1 with 75 segs, 8 bands. Hemoglobin and hematocrit were normal. A urine screen for THC was positive. A lithium level was 5.5 (normal 0.5 to 1.2). The patient admitted to taking more lithium and perphenazine "to feel better" and to "alleviate" some of his guilty feelings. He was unable to give any clarification on how much and over how long a period of time he had done this. Examiners noted that the patient was becoming more confused and lethargic and on the verge of falling asleep. At that time, the patient was transferred from the psychiatric service to the general medicine service. Forced diuresis was begun with normal saline and bicarbonate in an attempt to lower the serum lithium level.

Over the next two days, the patient’s lithium level declined to more normal levels. The patient remained to a small degree confused and ataxic but otherwise he responded to stimuli. On the third hospital day, the patient was found in a catatonic state with waxy flexibility. The patient at this point was nonverbal and was hyper-reflexic. The patient was transferred to the intensive care unit for emergent dialysis. Shortly after arrival to the ICU, the patient was found to be in respiratory distress and then proceeded to have a tonic-clonic seizure. The patient was intubated, loaded with Dilantin and started on a QD dose. He was hemodialyzed for 6 hours and again for 6 hours the next day with improvement of his lithium level. A head CT was normal and an EEG was consistent with a toxic encephalopathy.

With return of the patient’s lithium levels towards normal levels, his mental status began to improve. He was weaned off of the ventilator and eventually extubated. The patient was re-assessed and appeared to be at his baseline level of functioning. He was oriented and was responding appropriately to questions. Plans were made to transfer the patient out of the ICU when the patient suddenly coded and expired after a prolonged resuscitation attempt.

Discussion

Carl Lange and John Aulde first noted lithium salts to have mediating effects on mania and depression in the 1880s when they found that in certain patients for whom lithium was a treatment for gout, mania and depression seemed to be controlled. The use of lithium in psychiatry was uncommon until the 1950s when a series of clinical studies led to the discovery of lithium as an effective agent in the treatment of manic-depressive illness. It is now widely used as the drug of choice in those patients with bipolar disorder and has been used in some cases as a therapy for alcoholism, schizoaffective disorders, and even cluster headaches. The entry pathway of lithium into cells is unknown although sodium transport pathways such as the Na/K ATPase and sodium co-transporters have been implicated. The mechanism of lithium action is likewise still not clear although it is felt that lithium may inhibit the cAMP pathway by inhibiting activation of adenylyl cyclase.

The kidney is essentially the exclusive handler of lithium. As a non-protein bound substance, lithium is freely filtered in the glomerulus. In the proximal tubule it is treated as sodium would be treated. Thus states of volume depletion such as dehydration can increase lithium levels. Any drug that alters renal function can potentially lead to lithium toxicity. Agents that are commonly implicated in lithium toxicity include ACE inhibitors, NSAIDs, and thiazide diuretics.

Despite its therapeutic value, the use of lithium is accompanied by the dangers of a very narrow therapeutic window. Accepted therapeutic levels range from 0.6 to 1.5 mEq/L although 1.2 mEq/L is the level considered to be maximally beneficial for those patients with bipolar disorders. Lithium toxicity, which is most commonly characterized by varying degrees of altered mental status, is stratified into three categories: acute, acute on chronic, and chronic. Acute poisoning occurs in those individuals who are not being treated on lithium - for example, an accidental ingestion. Toxicity in these individuals tends to be milder because of a shorter lithium elimination half-life in those never exposed to lithium previously. Acute on chronic lithium toxicity is defined as toxicity in those patients being treated with lithium who take an overdose. Chronic lithium toxicity occurs in patients whose lithium dosage has been increased or whose renal function has declined, causing an increase in serum lithium levels. Lithium toxicity can be further classified into the following categories: mild, moderate, and severe. Mild symptoms include lethargy and drowsiness, hand tremors, weakness, and gastrointestinal symptoms. Moderate toxicity is characterized by confusion, slurred speech, nystagmus, ataxia, and EKG changes such as flat or inverted T waves. Severe toxicity can be lif,n between lithium levels and severity of symptoms can vary widely and often management of lithium toxicity is primarily based on clinical presentation.

Management of lithium toxicity depends on the degree of impairment. A basic work-up in those cases where lithium toxicity is suspected includes a serum lithium level and a metabolic profile. If there is a definite alteration in mental status, the airway should be protected. If caught early enough, an NG tube can be placed and gastric lavage can be performed. The use of charcoal is generally not of use because of its failure to bind lithium. Some studies however have recommended the use of polyethylene glycol as a medium to remove unabsorbed lithium ions in the GI tract. In addition, normal saline should be started intravenously to maintain urine output and assist the kidney in clearing lithium.

In more severe cases of lithium toxicity, such as in the patient described above, hemodialysis is the primary modality for clearance of lithium from the systemic circulation. Hemodialysis is the modality of choice in those patients who exhibit a detioration in mental status, seizure activity, renal failure or respiratory failure. However, in those patients whose lithium excretion is noted to be impaired by monitoring serial lithium levels, even if they may not manifest more severe signs of toxicity, hemodialysis should also be preformed. Hemodialysis can reduce plasma lithium by 1 mEq/L per 4 hours of treatment. Lithium levels can often rebound after hemodialysis as intracellular lithium re-enters the blood stream.

The patient described in this case was a good example of the difficulty in choosing the correct treatment modality for lithium toxicity. Although the patient, who must be assumed to have been on lithium chronically, had a markedly elevated lithium level, he did not manifest any of the severe neurological symptoms one might expect at such a high level. However, as his level came down with hydration, he began to manifest more of the severe symptoms that one ordinarily would not expect at such a level.

References

Reeves RR, Pendarvis BS, Kimble R: Unrecognized Medical Emergencies Admitted to Psychiatric Units. American Journal of Emergency Medicine 18: 390-393.

Timmer RT, Sands JM: Lithium Intoxication. Journal of the American Society of Nephrology 10: 666-674, 1999.

Albany Medical Center
43 New Scotland Avenue
Albany, New York 12208

E-mail the AMC Webmaster: Webmaster@mail.amc.edu

See your health care provider for specific medical advice.
AMC takes no responsibility for content  provided at external link sites.
Copyright, 1999-2001, Albany Medical Center.  All Rights Reserved