Case of Severe Acute-on-Chronic Lithium Intoxication with 8.6 mmol/l and Prompt Hemodialysis.

Lithium has been the gold standard in the long-term treatment of bipolar disorder for more than 40 years 1. Due to a narrow therapeutic index lithium intoxication still is a common but potentially avoidable clinical problem 2. The possibility of SILENT-syndrome (syndrome of irreversible lithium-effectuated neurotoxicity) illustrates that prevention and optimal treatment of lithium intoxication is vitally important 3.

Is Capillary Electrophoresis a New Tool to Monitor Acute Lithium Poisoning in Human?†.

A 38-year-old man was admitted in the intensive care unit (ICU) after supposed ingestion of 504 sustained-release tablets of Theralithe™ corresponding ~200 g of lithium carbonate. At the admission, ~19.5 h after ingestion, the patient was conscious with trembling limbs, intense thirst, profuse sweats and vomiting and lithium serum concentration was 14.2 mmol/L. Toxicological screenings performed in urine and serum, were negative. Patient was treated with continuous extrarenal epuration by continue veno-venous hemodiafiltration starting (CCVHDF) 24 h post-admission and was carried on until 64 h. After 11 days in ICU, the patient was dismissed to the service without sequelae, and transferred to a psychiatric unit. To follow lithium concentrations in serum, urines and dialysates, we developed a simple, rapid and reliable method by capillary zone electrophoresis (CZE). Separation was achieved in 7 min. The method was linear between 0.14 and 1.44 mmol/L for serum samples, and between 0.07 and to 1.44 mmol/L for urines and dialysates. Limits of quantification were 0.15 mmol/L and 0.07 mmol/L for serum and others fluids, respectively. Intra- and inter-day precisions expressed as CV were systematically inferior to 12.1% for serum and 8.2% for other fluids. Results obtained regarding precision, accuracy, recovery and stability were satisfying, with recoveries ranging from 91.0 to 102.0%. Serum, urine and dialysate samples were measured using CZE and flame photometry. We observed a strong correlation between both methods as assessed by linear regression and Bland-Altman analysis. For the intoxicated patient, the assay was successfully applied to serum, urine and dialysates to determine the amount of lithium present in circulation and excreted. Lithium amounts in dialysates were estimated to correspond to 89% of total lithium excreted during CCVHF session while urine excretion account only for 11%.

[Role of hemodialysis in the management of acute lithium intoxication]. / Place de l'hémodialyse dans la prise en charge de l'intoxication aiguë au lithium.

We report the case of a 47-years old patient, traited with lithium for manic-depressive psychosis over a period of twenty and admitted to hospital with a disorder of consciousness after suicide attempt with lithium overdose (ingestion of 30 tablets of Téralithe(®) LP 400, delayed action galenic forms corresponding to 12 g of lithium carbonate), clinically improved after three hemodialysis sessions. This study illustrates the therapeutic role of hemodialysis in voluntary intoxications with extended release lithium even a week after the ingestion and the therapeutic insufficiency of a single hemodialysis session.

A case of lithium intoxication induced by an antihypertensive angiotensin 1 subtype-specific angiotensin II receptor blocker in an elderly patient with bipolar disorder and hypertension.

Lithium carbonate is considered to be a first-line treatment for bipolar disorder; however, this drug has a narrow therapeutic window, and lithium intoxication is commonly induced by various drugs interaction and situations. We herein report a case of lithium intoxication induced by the administration of an antihypertensive agent targeting the angiotensin 1 (AT1) subtype of the angiotensin II receptor in a 65-year-old woman with a 40-year history of bipolar disorder type 1, and 1-year history of essential hypertension. Her bipolar disorder had been well-controlled with 600 mg/day of lithium carbonate for more than 10 years. She was later diagnosed with hypertension and the AT1 receptor blocker, azilsartan was thereafter administrated on a daily basis. After 3 weeks of azilsartan administration, she presented with progressive action tremor and showed a gradual deterioration of her physical state. Four months after the start of azilsartan administration, she presented with alternating episodes of diarrhea and constipation. Two weeks before admission to our hospital, she presented with mild consciousness disturbances, myoclonus, truncal ataxia, and appetite loss. She was diagnosed to have lithium intoxication based on an elevated serum lithium concentration of 3.28 mEq/l.It is therefore important to evaluate the serum lithium concentration after the administration of antihypertensive agents, and consider lithium-antihypertensive agent interactions when selecting antihypertensive agents in elderly patients receiving long-term lithium carbonate treatment.

Electrocardiac effects associated with lithium toxicity in children: an illustrative case and review of the pathophysiology.

Lithium is a potent psychotherapeutic agent that has gained wide acceptance in paediatrics, especially as adjunct treatment for severe behavioural, anxiety, and attention-deficit hyperactivity disorders, along with bipolar conditions. Its cardiac toxicity has been well-documented in adults; however, information is limited regarding lithium's effects on the heart in children. Therefore, paediatric cardiologists following-up children on lithium therapy should be cognizant of the cardiac side-effects and pathophysiology associated with this drug. In this manuscript, we used an illustrative case of a child who presented with lithium poisoning, in order to highlight adverse clinical manifestations that can arise from this medication. The cardiac cell membrane is thought to be the primary site of lithium's action. Thus, we reviewed lithium's effects on membrane electrogenic pumps and channels involved in the distribution and passage of sodium, potassium, and calcium across the sarcolemma, as these ions, and their associated currents, are the primary determinates of the action potentials underlying auto-rhythmicity and contractile activity of the heart.

Hemodialysis for lithium poisoning.

BACKGROUND: Lithium salts, particularly lithium carbonate, are frequently used to treat bipolar disorder and mania. Lithium poisoning, which can occur as a result of reduced renal elimination, prescribing error, drug-drug interactions, or deliberate overdosage, produces neurologic injury that can be permanent. Hemodialysis is often recommended to treat lithium poisoning. Although hemodialysis clearly enhances the elimination of lithium, it is unclear whether this translates into improved patient outcomes. Evidence from observational studies, generally of low methodological quality, shows similar outcomes in patients managed with or without the use of hemodialysis. OBJECTIVES: To determine whether hemodialysis, applied in addition to standard therapy, reduces the likelihood, severity, or duration of neurological sequelae following lithium poisoning. SEARCH METHODS: We ran the search on 15 May 2015. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase Classic+Embase (OvidSP), CINAHL Plus, clinical trials registers and four other databases. We screened the reference lists of relevant studies, textbook chapters, and review articles, and performed a Google search to identify grey literature. SELECTION CRITERIA: In the context of this review, hemodialysis was defined as any extracorporeal technique to filter and extract toxicants from the serum, including all forms of hemodialysis, hemofiltration, and continuous renal replacement techniques, but not peritoneal dialysis. We included any clinical trials in which patients were randomly allocated to receive, or not receive, hemodialysis in addition to standard care for lithium poisoning. DATA COLLECTION AND ANALYSIS: Two authors reviewed the abstracts of all identified articles. If either author identified an article as potentially meeting the inclusion criteria, both authors reviewed the full text of the article. MAIN RESULTS: No randomized controlled trials of hemodialysis therapy for lithium poisoning were identified. AUTHORS' CONCLUSIONS: Although the use of hemodialysis to enhance the elimination of lithium in patients with lithium poisoning appears logical, there is no evidence from randomized controlled trials to support nor refute the use of hemodialysis in the management of patients with lithium poisoning.

Removal of toxic substances by a selective membrane plasma separator.

We devised a method of plasma exchange with dialysis (PED), in which selective plasma exchange (sPE) is performed using a selective membrane plasma separator (EC-2A) with an albumin-sieving coefficient of 0.3 while the dialysate flows outside the hollow fibers, and reported the usefulness of the system for treating acute liver failure. Thereafter, EC-4A with an albumin-sieving coefficient of 0.6 was developed, which was expected to be even more effective for removing protein-bound substances. In order to examine whether or not EC-4A might be applicable to blood purification therapy against drug poisoning, we compared the efficacies of sPE, PED, and direct hemoperfusion (DHP) using an activated carbon column for the removal of phenobarbital and lithium. Subjects undergoing the extracorporeal circulation study were assigned to the sPE group, PED group, or DHP group, and the changes in the blood concentrations of phenobarbital and lithium were measured over 180 min. A significant decrease of the phenobarbital concentration over time was seen in the PED group, as compared to that in the sPE group (P < 0.0001), while no significant difference in the concentration was observed between the PED and DHP groups. The PED group showed a significant decrease of the lithium concentration over time, as compared to the DHP group (P < 0.0001), while no significant difference in the concentration was observed between the PED and sPE groups. Thus, PED was as effective as DHP for removing phenobarbital and was as effective as sPE for removing lithium. These results suggest that PED therapy using EC-4A may be a feasible modality for the treatment of drug poisoning.

[Medication errors after hospitalisation due to multi-dose drug dispensing in the primary sector]. / Dosisdispensering som årsag til fejlmedicinering ved sektorovergang.

Multi-dose drug dispensing (MDDD) was introduced in Denmark in 2001 in order to minimize medication errors. In May 2010 44.500 Danish citizens received MDDD. We report two cases where MDDD in the primary sector led to medication errors after hospitalisation, the reason partly being difficulties in getting information on MDDD on admission, lack of knowledge on handling MDDD in hospital and inadequate communication between the primary and the secondary sector. These problems has until now been underestimated.

Comparison of intermittent haemodialysis, prolonged intermittent renal replacement therapy and continuous renal replacement haemofiltration for lithium toxicity: a case report.

This case report compares three types of renal replacement therapy for acute severe lithium toxicity and is the first to use prolonged intermittent renal replacement therapy (PIRRT). A peak lithium level of 13.2mmol/L was recorded after a 51- year-old man attempted suicide. He was treated with intermittent haemodialysis (IHD), PIRRT and continuous venovenous haemofiltration (CVVH) over 55 hours. Lithium clearance was shown to be comparable between IHD and PIRRT, both of which were superior to CVVH. Expected efficacy of treatment with a single daily session of PIRRT was higher than IHD or CVVH. PIRRT is a useful strategy for dialysis among patients with acute lithium intoxication.

Fatal lithium toxicity with therapeutic levels--a case report.

For nearly five decades now, lithium has been used as a drug for treatment of bipolar affective disorder [1]. Adverse effects of lithium have been reported, but still lithium continues to be an effective prophylactic agent for bipolar disorder. Serious and fatal toxicity can occur with levels of lithium considered to be in the therapeutic range [2, 3, 4, 5, 6]. We are reporting a patient who was on lithium for bipolar disorder and was admitted with a history of sudden collapse following vomiting, and sinus bradycardia with ST-T changes. The patient expired with levels of lithium being within therapeutic range.

[Difficulty in determining when to end continuous hemodialysis for lithium intoxication: case report].

The patient was a 26-year-old woman who ingested a total of 230 tablets, including 160 lithium carbonate tablets (200 mg), in a suicide attempt, and was brought to our hospital 5 hr later. After arriving at the hospital, her only complaint was mild nausea, and no neurological abnormalities or renal dysfunction was observed. We were unable to learn the blood concentration of lithium immediately. A forced diuresis was performed after admission, but the nausea persisted. Continuous hemodialysis (CHD) was performed for 23.5 hr starting 19 hr after ingesting the tablets because the patient had ingested a large amount of lithium carbonate, 32,000 mg. Since the nausea resolved after the CHD was started and no manifestations of lithium intoxication had developed as of 91 hr after ingestion, the patient was discharged. The blood lithium concentrations (mEq/L) revealed at a later date showed that the concentration 5 hr (at the time of the initial examination), 19 hr (start of CHD), 44.5 hr (end of CHD), and 91 hr after ingestion (at the time of discharge) was 4.08, 3.30, 1.09, and 0.38, respectively. Blood purification is said to be effective in treating serious lithium intoxication, but it is difficult to judge when to stop. A favorable outcome of treatment of acute lithium intoxication in a patient with normal renal function appears to have been achieved by performing CHD guided by the clinical manifestations, intravascular redistribution times, etc.

Severity (and treatment) of chronic lithium poisoning: clinical signs or lab results as a criterion?

A 60-year-old woman with a lithium intoxication presented initially to the emergency department with a Glasgow coma scale (GCS) of 15/15. With initial conservative treatment (hydratation) she developed coma, necessitating haemodialysis. During haemodialysis there was no clinical improvement although there was a drop in the serum lithium levels. However, neurological recovery occurred after the first haemodialysis session, while the Lithium level rose again. This case illustrates initial clinical deterioration despite decreasing lithium levels as well as consequent clinical improvement without drop in lithium levels. This case also illustrates the pharmacokinetic profile of lithium and supports the use of primarily clinical signs completed with serum levels of lithium to determine the severity of a lithium poisoning and the adequate therapy including dialysis.

Self-poisonings with tricyclic antidepressants and selective serotonin reuptake inhibitors in Tehran, Iran.

In a prospective hospital-based cohort study, we addressed the question of severity and outcome of antidepressant poisonings in patients who attended the Loghman-Hakim Hospital Poison Center, the only national center in Tehran dedicated for detoxification. The aim of the study was to find out if tricyclic antidepressant (TCA) intoxications require more therapeutic efforts than selective serotonin reuptake inhibitor (SSRI) intoxications. The study was applied over a 7-week period (28 March-20 May 2006). From 3578 intoxications, 334 patients with antidepressant or lithium self-poisoning were identified (9.3% of all poisoning cases; 233 females, 101 males; median age 24 years, min 13, max 70). Compared to SSRI single-substance intoxications (n=17), TCA single-substance intoxications (n=73) were associated with: (1) a significantly lower level of consciousness (P=0.005); (2) a significantly higher admission frequency (80.8 vs. 35.3%; P<0.001); and (3) a higher intubation frequency (13.7 vs. 0%; P=ns). SSRI multiple-substance intoxications were associated with a significantly lower level of consciousness than SSRI single-substance intoxications (P=0.042), while there was no significant difference between TCA multiple- and single-substance intoxications. This study suggests that an overdose with SSRIs results in a more favourable clinical outcome than an overdose with TCAs.

[Hospital pharmacists prevented advance of lithium intoxication through pharmaceutical interventions].

Lithium carbonate is used to treat depressive episodes in patients with manic depressive disorder. Lithium toxicity is closely related to serum levels of lithium, and can occur with doses of lithium carbonate close to those used in therapy. Herein we report a case in which pharmaceutical intervention led to a patient's early recovery. The patient was hospitalized with a complaint of dyspnea, and clinical findings revealed signs of bradyarrhythmia. We investigated the medications the patient brought with him and the record of his prescribed medications in his drug notebook. From this we found that he had been taking imidapril (an angiotensin-converting enzyme inhibitor) in addition to lithium carbonate, and surmised that lithium toxicity may have occurred from the drug interactions between the lithium carbonate and imidapril in this patient. To prevent the level of toxicity from advancing, we proposed to the physician in charge that the patient's serum lithium levels be measured immediately and that all drugs be discontinued. By receiving care centered on detoxification, the patient avoided measures such as placement of a permanent pacemaker and thereby made a quick recovery from a dangerous state. This is a good example of a case in which pharmaceutical intervention improved the patient's quality of life (QOL) and contributed to conserving limited medical resources. As shown by this case, regular checks of patients' current medications and drug notebooks at the time of hospitalization are an effective means of implementing pharmaceutical interventions that can contribute to medical care.

[Development of sustained vasodilatory shock and permanent loss of hearing after severe lithium carbonate poisoning]. / Udvikling af refraktaert vasodilatorisk shock og permanent høretab efter svaer lithiumforgiftning.

A case of severe lithium carbonate self-poisoning is described, presenting with sustained vasodilatory shock, DIC and neurologic manifestations. Lengthy and repeated haemodialysis was required to lower lithemia to non-toxic levels in accordance with which the haemodynamic instability and multi organ dysfunction ceased. The patient survived with marked loss of hearing, tinnitus and vertigo as the only sequelae. We discuss the mechanism of lithium's inhibitory effect on the phosphoinositide cascade as the possible explanation for the vasodilatory shock as well as the hearing deficiency.