Lithium Intoxication after Bariatric Surgery: A Case Report.

Bariatric surgery is a therapeutic option to treat obesity in (carefully selected) patients with psychiatric disorders. About half of the patients referred for bariatric surgery have a diagnosis of (at least one) mental disorder and most of them are treated with psychotropic drugs. This procedure may modify the bioavailability of drugs and lithium is no exception. However, although absorption seems to decrease in most drugs, in the case of lithium, there is a high risk of toxicity. In this article, we describe the case of a 44-year-old female patient with lithium intoxication after bariatric surgery. We conducted a review of the published clinical cases in the scientific literature about lithium toxicity after bariatric surgery, and we propose potential preventive clinical solutions. It is essential to increase awareness of changes to the absorption of psychotropic drugs in the post-surgery period, particularly in the case of lithium. Regular postoperative clinical and laboratory monitoring of lithium serum levels is strongly recommended.

A cirurgia bariátrica é uma opção terapêutica no tratamento da obesidade em doentes, selecionados cuidadosamente, com perturbação psiquiátrica. Cerca de metade dos doentes referenciados para cirurgia bariátrica têm diagnosticada, pelo menos, uma perturbação mental, estando a maioria medicada com psicofármacos. Este procedimento pode alterar significativamente a biodisponibilidade dos fármacos e o lítio não é exceção. Contudo, apesar da absorção parecer diminuir na maioria dos fármacos, no caso do lítio existe um elevado risco de toxicidade. Neste artigo, descreve-se o caso de uma doente de 44 anos com um quadro de intoxicação por lítio pós-cirurgia bariátrica. Realizou-se uma revisão dos casos clínicos descritos na literatura de toxicidade ao lítio pós-cirurgia bariátrica e apresentam-se potenciais soluções clínicas preventivas. É essencial uma maior consciencialização das alterações na absorção dospsicofármacos pós-cirurgia, particularmente no caso do lítio. Recomenda-se fortemente uma monitorização, de forma mais regular, pós-cirúrgica clínica e laboratorial dos níveis séricos de lítio.

[Extracorporeal renal replacement therapies in lithium intoxication].

Drug poisoning is a significant source of morbidity, mortality and health care expenditure worldwide. Lithium, methanol, ethylene glycol and salicylates are the most important ones, included in the list of poisons, that may require extracorporeal depuration. Lithium is the cornerstone of treatment for bipolar disorders, but it has a narrow therapeutic window. The therapeutic range is 0.6-1.2 mEq/L and toxicity manifestations begin to appear as soon as serum levels exceed 1.5 mEq/L. Severe toxicity can be observed when plasma levels are more than 3.5 mEq/L. Lithium poisoning can be life threatening and extracorporeal renal replacement therapies can reverse toxic symptoms. Currently, conventional intermittent hemodialysis (IHD) is the preferred extracorporeal treatment modality. Preliminary data with prolonged intermittent renal replacement (PIRRT) therapies - hybrid forms of renal replacement therapy (RRT) such as sustained low efficiency dialysis (SLED) - seem to justify their role as potential alternative to conventional IHD. Indeed, SLED allows rapid and effective lithium removal with resolution of symptoms, also minimizing rebound phenomenon.

Effect of age on the severity of chronic lithium poisoning.

Objectives: Severe lithium toxicity is commonly observed in older people. We aimed to determine the extent to which age is associated with increased severity of chronic lithium poisoning and of which a range of possible factors might explain the associations.Method: We did a retrospective review of patients aged ≥15 years old with serum lithium concentrations ≥1.3 mmol/L from three hospitals. Clinical details, treatment and outcomes were recorded. eGFR, creatinine and lithium clearance were calculated. The severity of lithium toxicity was graded into five categories (Amdisen score). ANOVA was used to quantify the association between age and severity. Spearman correlation coefficient was used to explore relationships between age and different factors expected to alter severity. Ordinal regression analysis was used to determine the interdependence of age and these factors and age on severity of lithium toxicity.Results: From 2008-2018, there were 242 patients with a median age of 56.5 years (IQR: 41-69). There were 156 females (64%). There was a statistically significant association between Amdisen severity scores and age (p = .0004). The median calculated eGFR was 65 mL/min/1.73 m2 (IQR: 41-91) with a corresponding estimated lithium clearance of 18 mL/min (IQR: 13.8-22.8). There was no correlation of age with initial serum lithium concentration (p = .76). There was a strong correlation between age and estimated lithium clearance (r = -0.72, 95% CI: -0.78 to -0.66, p < .001), lithium daily dose (r = -0.65, 95% CI: -0.72 to -0.57, p < .0001) and lithium concentration/dose (r = 0.62, 95% CI: 0.53-0.69, p < .0001). There was a weak correlation between age and infection (r = 0.18, 95% CI: 0.04-0.31, p = .009) and drug interactions (r = 0.25, 95% CI: 0.11-0.37, p = .0003). Ordinal regression indicated the independent predictors for severity of lithium toxicity were lithium concentration (p < .0001) and lithium clearance (p = .03) adjusted for age and dose.Conclusions: Despite lower lithium doses, older patients had more severe toxicity. Increased severity of lithium toxicity in the elderly is largely explainable by decreased lithium clearance from multiple factors such as age-related decline in renal function, drug interactions and infection.

Non accidental repeated lithium poisoning in a child: The role of hair analysis.

Non accidental intoxication due to child abuse is rare and its frequency is likely underestimated because it is difficult to diagnose. Here, we report a case of voluntary repeated exposure to lithium in an infant, for whom the clinical manifestations were convulsions. Toxicological analysis was very helpful for documenting lithium exposure during the assumed period of time. Interpreting the results of hair analysis, a simple and minimally invasive examination, is tricky at this age, but it can facilitate the differentiation of acute versus chronic exposure. Although infrequent and underestimated, lithium should be considered as a cause of intoxication in a previously healthy child with acute seizure.

Haemodialysis for lithium poisoning: Translating EXTRIP recommendations into practical guidelines.

OBJECTIVES: This study aimed to determine the impact on practice of applying the Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup criteria to lithium toxicity. METHOD: We retrospectively examined the medical records of patients from three hospitals who presented with chronic or acute on chronic lithium poisoning with a lithium concentration ≥1.3 mmol/L (2008-2018). We determined which criteria were met by patients and their subsequent course. We developed and validated a method to predict if lithium concentration would be >1mmol/L at 36 hours. RESULTS: There were 111 acute on chronic and 250 chronic lithium toxic patients. Nine patients (2.5%) were treated with haemodialysis. Six chronic patients had neurological sequelae. The "estimated lithium concentration at 36 hours > 1 mmol/L" criterion required pharmacokinetic calculations. A simple nomogram was developed using Estimated Glomerular Filtration Rate (eGFR) and lithium concentration. For chronic toxicity, the nomogram would have correctly predicted lithium concentration >1.4 mmol/L at 36 hours in all except two patients. If EXTRIP criteria were followed, dialysis would have been instituted for 211 patients (58%). However, only 51 patients with chronic toxicity fulfilled both a concentration and a clinical criterion. Late neurological sequelae were observed in five out of six patients who fulfilled a concentration and a clinical criterion on admission, with the sixth meeting these criteria shortly after admission. CONCLUSIONS: The EXTRIP criteria are too broad, but minor modifications allow haemodialysis to be targeted to those most at risk of sequelae. Most acute on chronic poisonings do not need haemodialysis, but it might shorten hospital stay in those with very high concentrations. The nomogram accurately predicts the fall in lithium concentration for chronic poisoning.

Neurotoxicity in chronic lithium poisoning.

BACKGROUND: Lithium-induced neurotoxicity typically occurs with chronic accumulation rather than following acute overdose. There is little emphasis in the literature on the protracted nature of lithium neurotoxicity long after the lithium concentration returns to the therapeutic range. AIMS: To characterise lithium neurotoxicity, with a view of increasing awareness of this important phenomenon. METHODS: This is a retrospective observational study of patients presenting with lithium-induced neurotoxicity over a 5-year period to a clinical toxicology unit. Patients were identified through the unit's database, and clinical notes were analysed. RESULTS: There were 22 patients, with a median age of 65 (range: 36-89) years. Six patients (27%) had previous lithium toxicity, and nine (41%) were regularly prescribed medications that impair lithium excretion. The median lithium concentration on presentation was 2.2 mmol/L, taking a median of 3 days to return to the therapeutic range. Reversible acute kidney injury was observed in 21 patients (95%) on presentation. The median length of stay was 13 (range: 3-95) days due mostly to delayed neurological recovery. Confusion was the predominant symptom, present in 21 (95%) patients, followed by tremors (18(82%)) and ataxia (16(73%)). Multiple investigations were performed to exclude delirium differentials, including 11 computed tomography (CT) and five magnetic resonance imaging (MRI) brain scans, all unremarkable. CONCLUSIONS: Lithium neurotoxicity has a prolonged course. Its severity correlates poorly with lithium concentrations, which normalise quickly. Most poisonings occur in elderly patients with acute kidney injury. Prolonged delirium often prompts multiple unnecessary investigations. Rationalisation of lithium therapy is important in elderly patients.

Compromiso de conciencia secundario a intoxicación por litio: reporte de un caso / Commitment of conscience secondary to lithium intoxication: case report

INTRODUCCIÓN: La intoxicación por litio (IL) es potencialmente grave. Destacan manifestaciones neurológicas, tales como deterioro cognitivo, síndrome cerebeloso y compromiso de conciencia (CC). En la literatura se han descrito secuelas permanentes secundarias a la IL, siendo importante el manejo precoz para prevenir una evolución tórpida de este cuadro. PRESENTACIÓN DEL CASO: Paciente de sexo femenino de 77 años con antecedentes de Trastorno Afectivo Bipolar (TAB), en tratamiento con Litio, inició cuadro de 5 días de evolución caracterizado por bradipsiquia, compromiso del estado general (CEG) y disminución de fuerza en extremidades inferiores. Evaluada por Neurología, se descartó patología cerebrovascular e infecciosa intercurrente, se midió litemia que resultó alterada. Se diagnosticó CC secundario a IL. Se indicó suspensión de fármaco y manejo de balance hidroelectrolítico. Evolucionó con daño neurológico de pronóstico incierto y fue dada de alta por Neurología. DISCUSIÓN: La intoxicación por litio debe sospecharse en cualquier paciente con alteración del estado de conciencia basal, que sea usuario de este medicamento. Pacientes que presentan IL requieren hospitalización para manejo de fluidos y electrolitos, monitorizando función renal y litemia. A nivel del sistema nervioso central (SNC) la IL puede dejar secuelas irreversibles, por lo que se recomienda un seguimiento regular de aquellos pacientes que sean usuarios de este medicamento, para evitar un deterioro clínico secundario a una intoxicación.

INTRODUCTION: (LI) can be potentially serious. Includes neurological manifestations such as cognitive impairment, cerebellar syndrome and compromise of consciousness (CC). In the literature have been described permanent sequelae secondary to intoxication by this drug, early management is important to prevent an undesirable evolution of this medical condition. CASE REPORT: 77-year-old female patient with a history of Bipolar Affective Disorder, under treatment with Lithium, began a 5-day history of bradypsychia, compromise of the general state and decrease strength in lower extremities. Evaluated by Neurology, ruled out cerebrovascular and infectious pathologies. Plasmatic lithium levels were obtained in altered range. CC secondary to LI was diagnosed. Drug suspension, fluid and electrolyte balance management were indicated. She evolved with neurological damage of uncertain prognosis and discharged from hospital. DISCUSSION: LI should be suspected in any patient with altered baseline consciousness, who is a user of this medication. Patients requires admission for fluid and electrolyte management, monitoring of renal function and plasmatic lithium levels. At the level of the central nervous system (CNS) IL can leave irreversible sequels, so it is recommended a regular monitoring of patients who are users of this drug, to avoid clinical deterioration secondary to intoxication.

Serum lithium levels and suicide attempts: a case-controlled comparison in lithium therapy-naive individuals.

BACKGROUND: Several epidemiological studies have shown the inverse association of lithium levels in drinking water and suicide rates; however, it is necessary to perform a clinical study dealing with individual patients. METHODS: We analyzed 199 patients including 31 patients with suicide attempts, 21 patients with self-harm, and 147 control patients. All were transferred to a university emergency department suffering from intoxication or injury, were aged 20 or more years, and were alive at the start of the study. The exclusion criteria consisted of suffering from schizophrenia and a past or present history of lithium therapy. These exclusions were applied because it is difficult to determine whether their suicide attempt was induced by the intent to end their life or by psychotic symptoms such as auditory hallucinations, and if the patient had received lithium therapy, the association between the small amount of lithium taken from drinking water and food and serum lithium levels cannot be detected. RESULTS: There was a significant difference (p = 0.043) between the three groups whereby patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.012) in males but not females. Multivariate logistic regression analysis with adjustment for age and gender revealed that patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.032, odds ratio 0.228, 95% CI 0.059-0.883). LIMITATIONS: The limitations of the present study are the nature of observational research which cannot reveal a causal relationship and the relatively small number of subjects. CONCLUSIONS: The present findings suggest that higher serum lithium levels may be protective against suicide attempts in lithium therapy-naive individuals.

Predicting serum drug level using the principles of pharmacokinetics after an overdose: a case of lithium overdose.

OBJECTIVE: In cases of drug overdose, clinicians often find it challenging to predict serum drug level and decide the optimum time for recommencing the overdosed drug. METHOD: This paper describes how to predict serum drug level using the principles of pharmacokinetics. RESULTS: The proposed method and recommencement of the overdosed drug is demonstrated using a clinical case of lithium overdose. CONCLUSION: The proposed method can assist clinicians in predicting serum drug levels and deciding the optimum time for recommencing the overdosed drug safely. Therefore, it may reduce unnecessary repeat serum drug level procedures.

Lithium Poisoning.

Lithium is a commonly prescribed treatment for bipolar affective disorder. However, treatment is complicated by lithium's narrow therapeutic index and the influence of kidney function, both of which increase the risk of toxicity. Therefore, careful attention to dosing, monitoring, and titration is required. The cause of lithium poisoning influences treatment and 3 patterns are described: acute, acute-on-chronic, and chronic. Chronic poisoning is the most common etiology, is usually unintentional, and results from lithium intake exceeding elimination. This is most commonly due to impaired kidney function caused by volume depletion from lithium-induced nephrogenic diabetes insipidus or intercurrent illnesses and is also drug-induced. Lithium poisoning can affect multiple organs; however, the primary site of toxicity is the central nervous system and clinical manifestations vary from asymptomatic supratherapeutic drug concentrations to clinical toxicity such as confusion, ataxia, or seizures. Lithium poisoning has a low mortality rate; however, chronic lithium poisoning can require a prolonged hospital length of stay from impaired mobility and cognition and associated nosocomial complications. Persistent neurological deficits, in particular cerebellar, are described and the incidence and risk factors for its development are poorly understood, but it appears to be uncommon in uncomplicated acute poisoning. Lithium is readily dialyzable, and rationale support extracorporeal treatments to reduce the risk or the duration of toxicity in high-risk exposures. There is disagreement in the literature regarding factors that define patients most likely to benefit from treatments that enhance lithium elimination, including specific plasma lithium concentration thresholds. In the case of extracorporeal treatments, there are observational data in its favor, without evidence from randomized controlled trials (none have been performed), which may lead to conservative practices and potentially unnecessary interventions in some circumstances. More data are required to define the risk-benefit of extracorporeal treatments and their use (modality, duration) in the management of lithium poisoning.

Lithium poisoning in the intensive care unit: predictive factors of severity and indications for extracorporeal toxin removal to improve outcome.

CONTEXT: Lithium is responsible for life-threatening poisoning, not consistently improved by extracorporeal toxin removal (ECTR). OBJECTIVE: Our aim was to identify predictive factors on admission of poisoning severity and based on an evaluation of practice, report indications for ECTR susceptible to improve outcome Methods: We performed a retrospective cohort study including all lithium-poisoned patients admitted to the ICU in a university hospital. The usual clinical, biological and toxicological variables were collected. Poisoning severity was defined by seizures, catecholamine infusion, mechanical ventilation >48 h and/or fatality. Univariate followed by multiple logistic regression analyses were performed to identify prognosticators of poisoning severity and ECTR use. RESULTS: From 1992 to 2013, 128 lithium-poisoned patients including acutely (10%), acute-on-chronically (63%) and chronically poisoned patients (27%) were included. The presumed ingested dose of lithium was 17.0 g [8.0-24.5] (median [25th-75th percentiles]). Serum lithium concentrations were 2.6 mmol/l [1.5-4.6], 2.8 mmol/l [1.8-4.5] and 2.8 mmol/l [2.1-3.0] on admission, peaking at 3.6 mmol/l [2.6; 6.2], 4.3 mmol/l [2.4; 6.2] and 2.8 mmol/l [2.1; 3.1] in the three groups, respectively. Severe poisoning occurred in 48 patients (38%) including four fatalities. Using the regression analysis, predictive factors of poisoning severity were Glasgow coma score ≤10 (Odds ratio (OR), 11.1; 95% confidence interval (CI), [4.1-33.3], p < 0.0001) and lithium concentration ≥5.2 mmol/l (OR, 6.0; CI, [1.7-25.5], p = 0.005). Ninety-eight patients (77%) developed acute kidney injury according to KDIGO criteria and 22 (17%) were treated with ECTR. Peak lithium concentration ≥5.2 mmol/l (OR, 22.4; CI, [6.4-96.4]; p < 0.0001) and peak creatinine concentration ≥200 µmol/l (OR, 5.0; CI, [1.4-19.2]; p = 0.01) were associated with ECTR use. Only 21/46 patients who presented one of these two criteria were actually treated with ECTR. More significant neurological impairment persisted on discharge in patients not treated with ECTR (p = 0.0007) despite not significantly shorter length of ICU stay. CONCLUSIONS: Lithium poisoning is responsible for severe impairments but rare fatalities. Severity can be predicted on admission using Glasgow coma score and lithium concentration. Our results suggest that ECTR could be indicated if serum lithium ≥5.2 mmol/l or creatinine ≥200 µmol/l.

Oral Exposure of a Child to a Lithium Ion Battery.

Battery exposure has the potential for severe morbidity and possible mortality. Accidental exposure is rising with the increased use of button batteries, and young children and older adults are at highest risk for accidental exposure. The purpose of this paper is to report a case of mouth exposure to a lithium ion battery in a boy. A review of the current literature on incidence, diagnosis, and outcomes of battery exposure is presented. When symptoms such as diarrhea, vomiting, and abdominal distress of non-specific origin are present, battery ingestion should be included in the differential diagnosis. Dentists may be the first health professionals to encounter battery exposure, especially in the case of mouth exposures. Knowledge of signs and symptoms are necessary to properly diagnose and refer for medical management.

Extracorporeal Treatment for Lithium Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup.

The Extracorporeal Treatments in Poisoning Workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments in poisoning. Here, the EXTRIP workgroup presents its recommendations for lithium poisoning. After a systematic literature search, clinical and toxicokinetic data were extracted and summarized following a predetermined format. The entire workgroup voted through a two-round modified Delphi method to reach a consensus on voting statements. A RAND/UCLA Appropriateness Method was used to quantify disagreement, and anonymous votes were compiled and discussed in person. A second vote was conducted to determine the final workgroup recommendations. In total, 166 articles met inclusion criteria, which were mostly case reports, yielding a very low quality of evidence for all recommendations. A total of 418 patients were reviewed, 228 of which allowed extraction of patient-level data. The workgroup concluded that lithium is dialyzable (Level of evidence=A) and made the following recommendations: Extracorporeal treatment is recommended in severe lithium poisoning (1D). Extracorporeal treatment is recommended if kidney function is impaired and the [Li(+)] is >4.0 mEq/L, or in the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of the [Li(+)] (1D). Extracorporeal treatment is suggested if the [Li(+)] is >5.0 mEq/L, significant confusion is present, or the expected time to reduce the [Li(+)] to <1.0 mEq/L is >36 hours (2D). Extracorporeal treatment should be continued until clinical improvement is apparent or [Li(+)] is <1.0 mEq/L (1D). Extracorporeal treatments should be continued for a minimum of 6 hours if the [Li(+)] is not readily measurable (1D). Hemodialysis is the preferred extracorporeal treatment (1D), but continuous RRT is an acceptable alternative (1D). The workgroup supported the use of extracorporeal treatment in severe lithium poisoning. Clinical decisions on when to use extracorporeal treatment should take into account the [Li(+)], kidney function, pattern of lithium toxicity, patient's clinical status, and availability of extracorporeal treatments.