Plasma Lithium Research Articles

A-017 Clinical Performance Evaluation of the Atellica IM High-Sensitivity Troponin I Assay to Aid in Risk Stratification for All-Cause Mortality and Major Adverse Cardiac Events

Abstract Background Cardiac troponin I (cTnI) is the only troponin isoform present in the myocardium, where it binds to actin and inhibits actin and myosin interaction. Upon myocardial injury, cTnI is released into circulation and serial measurements can be used to aid in the diagnosis of acute myocardial infarction (AMI). In addition, in patients presenting with signs and symptoms of acute coronary syndrome (ACS), elevated cTnI levels provide useful prognostic information relative to short and long-term risk of all-cause mortality (ACM) and major adverse cardiac events (MACE). The objective of this study was to evaluate the clinical performance of the Atellica® IM TNIH assay to aid in risk stratification for ACM/MACE*. Methods Patients from 29 emergency departments (ED) across the United States presenting with signs and symptoms suggestive of ACS were followed for 30-, 90-, and 365-day progression to ACM/MACE (consisting of myocardial infarction, urgent revascularization, cardiac death, or heart failure hospitalization). At each timepoint, the risk (cumulative incidence) and hazard ratios were calculated for populations with baseline cTnI levels ≤ or > the 99th percentile value. Kaplan-Meier curves were generated to display the absolute risk (cumulative incidence) of ACM/MACE outcomes. Analyses were performed for all enrolled patients (entire population) and separately for the entire population excluding those with an adjudicated AMI at presentation. Analyses were performed separately for both serum and plasma (lithium heparin) sample types. Results For the Entire Population cohort, the binary baseline TNIH result (TNIH > overall 99th percentile or ≤ overall 99th percentile) was significantly associated with 30-, 90-, and 365-day cumulative ACM/MACE (p-value<0.0125) for both plasma and serum samples. For plasma samples, risk difference increased from 6.27% at day 30 to 19.62% at day 365. For serum samples, risk difference increased from 6.24% at day 30 to 18.71% at day 365. Cox proportional hazard regression analysis compared the TNIH 99th percentile groups in their hazard of experiencing an ACM/MACE event in the 30-, 90-, and 365-days post ED presentation. For plasma samples, the hazard of ACM/MACE for subjects with cTnI values above the TNIH 99th percentile was relatively constant at each follow-up interval as more than double the rate of subjects below the 99th percentile; hazard ratios ranged between 2.81 (p-value<0.0001) and 3.49-fold (p-value<0.0001) for the three follow up visits. For serum samples, the hazard ratios were between 2.69 (p-value<0.0001) and 3.28-fold (p-value<0.0001) for the three follow up visits. Similar results were obtained for the Entire Population Excluding Subjects with Adjudicated AMI During Initial Presentation cohort. Conclusions The Atellica IM TNIH assay can be used in the detection of myocardial injury and can aid in risk stratification for 30-, 90-, and 365-day all-cause mortality (ACM) and major adverse cardiac events (MACE) in patients presenting with signs and symptoms suggestive of acute coronary syndrome (ACS). *This prognostic claim is not available in the United States.

Recién nacida con litemia en rango tóxico. ¿Debemos retirar la lactancia materna?

Lithium is a common part of the treatment for bipolar disorder. It is excreted through breast milk, and traditionally, mothers undergoing this treatment were advised to discontinue breastfeeding due to the potential serious adverse effects of this medication on the infant. More recently, it has been demonstrated that plasma lithium levels in exposed children are generally low and well tolerated, so, in selected cases, breastfeeding can be maintained, and close clinical and analytical monitoring of the child can be conducted, including measurement of thyroid and renal function, and serial lithium levels. We present a clinical case of a full-term newborn, born to a mother with bipolar disorder receiving lithium treatment, exclusively breastfed on demand, who in the second week of life showed toxic levels of lithium in plasma with no symptoms. Careful investigation of the case revealed that the elevated lithium levels were falsely elevated due to incorrect collection of the blood sample in a container containing lithium-heparin as an anticoagulant. The circumstances of the case will be reviewed as well as current recommendations on lithium intake by mothers and breastfeeding of their children.

The correlation between single and mixed trace elements exposure in systemic lupus erythematosus: A case-control study

BackgroundRecent studies have shown an association between trace elements and systemic lupus erythematosus (SLE), but the relationship between trace elements and SLE is still unclear. This study aims to determine the distribution of plasma trace elements in newly diagnosed SLE patients and the association between these essential and toxic element mixtures and SLE. MethodsIn total, 110 SLE patients and 110 healthy controls were included. Blood samples were collected. 15 plasma trace elements were quantified using an inductively coupled plasma mass spectrometer (ICP-MS). Multivariate logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) are used to analyze the association between single and mixed exposure of elements and SLE. ResultsThe logistic regression model shows that, plasma lithium (Li) [OR (95 % CI): 1.963 (1.49–2.586)], vanadium (V) [OR (95 % CI): 2.617(1.645–4.166)] and lead (Pb) [OR (95 % CI): 1.603(1.197–2.145)] were positively correlated with SLE, while selenium (Se) [OR (95 % CI): 0.055(0.019–0.157)] and barium (Ba) [OR (95 % CI): 0.792(0.656–0.957)] had been identified as protective factors for SLE. RCS results showed a non-linear correlation between the elements Li, V, Ni, copper, Se, rubidium and SLE. In addition, WQS regression, qgcomp, and BKMR models consistently revealed significant positive effects of plasma Li and Pb on SLE, as well as significant negative effects of plasma Se. ConclusionsExposure to heavy metals such as Li and Pb is significantly positively correlated with SLE, but Se may be protective factors for SLE. In addition, there is a nonlinear correlation between the elements Li and Se and SLE, and there are complex interactions between the elements. In the future, larger populations and prospective studies are needed to confirm these associations.

A Comparison Study: Possible Bias in Troponin I Measurement Obtained with a Point of Care Testing and a Central Laboratory Analyzers Employing Different Biological Matrices and Anticoagulants.

high-sensitive cardiac TroponinI (hs-cTnI) is widely used for diagnosis of acute coronary syndromes. The latest recommendation for hs-cTnI determination is the protocol 0-1 h finalized to improve the rule out accuracy of the test. A Point of Care Testing able to guarantee these performances could be very useful due to reducing the turnaround time and ruling out patients suspected of ACS, especially by using biological matrices that are not required for centrifuge. The aim of our work is to compare the results for hs-cTnI obtained using different biological matrices and anticoagulants, obtained between Atellica® VTLi hs-cTnI POCT and Access AccuTnI+3 DxI800 performances, in order to establish a possible bias derived directly from these pre-analytical conditions. Li-heparinized pool samples were primary employ for hs-cTnI with Atellica® VTLi as whole blood, then centrifuged and tested on Atellica® VTLi and DxI800. K3EDTA pool samples were centrifuged and measured on DxI800 too. A comparison of methods was performed according to CLSI_EP-09A2 protocol. Constant and proportional errors were investigated with Deming regression. Bias between methods was evaluated with the Bland Altman test. comparing whole blood lithium heparin results obtained with Atellica versus lithium heparin and K3EDTA plasma tested on DxI 800, the Deming regression revealed a proportional error, whereas in both cases Bland Altman highlighted a minimal underestimation. A similar performance was revealed when considering plasma lithium heparin tested on Atellica versus lithium heparin and K3EDTA plasma obtained with DxI800, confirming the same underestimation. Considering values close to the cut off, no significant differences were found. in the laboratory, the estimation of the bias of two different analyzers is pivotal. Once more this is crucial when different biological matrices and anticoagulants are employed for the analysis. Our study demonstrates that no significant differences among the two matrices are present when comparing Atellica and DxI800 performances.

Low exposition to lithium prevents nephrogenic diabetes insipidus but not microcystic dilations of the collecting ducts in long-term rat model.

Lithium induces nephrogenic diabetes insipidus (NDI) and microcystic chronic kidney disease (CKD). As previous clinical studies suggest that NDI is dose-dependent and CKD is time-dependent, we investigated the effect of low exposition to lithium in a long-term experimental rat model. Rats were fed with a normal diet (control group),with the addition of lithium (Li+ group), or with lithium and amiloride (Li+/Ami group) for 6 months, allowing obtaining low plasma lithium concentrations (0.25 ± 0.06 and 0.43 ± 0.16 mmol/L, respectively). Exposition to low concentrations of plasma lithium levels prevented NDI but not microcystic dilations of kidney tubules, which were identified as collecting ducts (CDs) on immunofluorescent staining. Both hypertrophy, characterized by an increase in the ratio of nuclei per tubular area, and microcystic dilations were observed. The ratio between principal cells and intercalated cells was higher in microcystic than in hypertrophied tubules. There was no correlation between AQP2 messenger RNA levels and cellular remodeling of the CD. Additional amiloride treatment in the Li+/Ami group did not allow consistent morphometric and cellular composition changes compared to the Li+ group. Low exposition to lithium prevented overt NDI but not microcystic dilations of the CD, with differential cellular composition in hypertrophied and microcystic CDs, suggesting different underlying cellular mechanisms.

Understanding Lithium intoxication in Bipolar Disorder: a comparative analysis and clinical implications

IntroductionLithium treatment is a proven method for bipolar disorder management, but its narrow therapeutic range and the risk of severe side effects, including lithium intoxication, pose significant clinical hurdles. Lithium intoxication, a potentially life-threatening complication, can occur during treatment, raising ongoing questions about its clinical factors, risk elements, and best practices for management.ObjectivesOur objective is a comparative analysis between patients who have experienced lithium intoxication and those who have not, aiming to identify influencing factors and enhance clinical care.MethodsWe collected demographic data, age at lithium treatment initiation, treatment duration, therapeutic adherence, Mental Health consultations, and lithium level monitoring from 14 individuals requiring clinical attention due to lithium intoxication and 14 patients with similar gender, age, and diagnosis with lithium treatment but without intoxication during four years of follow-up.ResultsRegarding the results, the age of onset of lithium treatment in patients with lithium intoxication was 30.2 years (SD=8), and the duration of lithium treatment averaged 11.1 years (SD=8.8), which did not significantly differ from the control group with ages of onset at 38.1 years (SD=15.1) and treatment duration of 9.27 years (SD=8.8), respectively. Lithium intoxication patients developed severe complications, including hospitalizations in medical-surgical units, the necessity for dialysis, and death, one fatal case. Although therapeutic adherence to lithium, measured through pharmaceutical dispensation, exceeded 90% and was comparable in both groups, patients affected by lithium intoxication exhibited a significantly higher treatment discontinuation rate (OR 32.5; 95% CI, 3.1 to 337.8) during the follow-up period. Patients who experienced lithium intoxication had an average of psychiatric consultations every 11.2 months (SD=13.4), with 35.7% not attending at least once a year, while the control group had an appointment every 5.31 months (SD=2.7) (p > 0.05). Lastly, despite both groups having a similar frequency of plasma lithium level monitoring, occurring approximately every 5.5 months (SD=2.6) and 7.8 months (SD=4.8), respectively, in 28.5% of those who suffered from lithium intoxication did not undergo any monitoring for periods exceeding 18 months (p < 0.05).ConclusionsOur research highlights the significance of delivering thorough clinical care and continuous monitoring to patients receiving lithium treatment for bipolar disorder. Ensuring effectiveness therapeutic adherence and maintaining strict monitoring of lithium levels are critical factors that significantly enhance treatment safety. Appropriate management has the potential to improve the quality and safety of care for people with bipolar disorder who are dependent on lithium therapy.Disclosure of InterestNone Declared

Exploring the clinical factors affecting lithium dose and plasma level and the effect of brand.

Optimal use of lithium involves adjustment of the dose, to keep the plasma level within the narrow, recommended range. Brand-specific prescribing has long been considered critical to achieving this aim, but this is a convention based on very limited data. To explore the effect of selected demographic and clinical factors on the relationship between lithium dose and plasma level and determine whether there is an independent effect of lithium brand. Analysis of clinical audit data collected in 2023 as part of a quality improvement programme addressing the use of lithium, conducted by the Prescribing Observatory for Mental Health. Data were collected from clinical records using a bespoke proforma, submitted online and analysed using SPSS. Data were submitted for 4405 patients who had been prescribed solid-dosage formulations of lithium for more than a year. Priadel® was prescribed for 3722 (84%) of these patients, Camcolit® for 112 (2.5%) and the prescription was written generically for 554 (12.5%). Compared with Priadel, where Camcolit was prescribed, the mean daily dose was 10% higher and the mean plasma lithium level was 11% higher. A multivariable analysis was conducted to explore the relationship between selected clinical variables and maintenance lithium dose. This found that in 4213 patients whose most recent plasma lithium level was between 0.3 and 1.19 mmol/L, the variables age, sex, ethnicity, psychiatric diagnosis and the severity of chronic kidney disease were independently associated with dose while the brand of lithium prescribed was not. Our findings replicate those of previous studies with respect to the demographic and clinical variables that can be expected to influence lithium dosage in routine clinical practice. This reinforces the need to titrate the dosage for each individual patient, to achieve and maintain the target plasma level. However, the findings suggest that the Priadel and Camcolit brands of lithium are essentially interchangeable.

Lithium Cholesterol Sulfate: A Novel and Potential Drug for Treating Alzheimer's Disease and Autism Spectrum Disorder.

Recent studies have shown that lithium treatment can reduce symptoms of Alzheimer's disease (AD) and Autism Spectrum Disorder (ASD). However, the present lithium salts clinically available have serious short-term and long-term side effects which requires frequent monitoring of blood chemistry and plasma lithium levels so as to avoid toxicity. Consequently, there is a demand for a safer and more effective lithium formulation to treat these diseases. Hence, we firstly synthesized lithium cholesterol sulfate (LiCS) and compared its pharmacological effects with that of lithium chloride (LiCl) and sodium cholesterol sulfate (NaCS) on markers of neurodegenerative disease in cell cultures. LiCS was more potent than LiCl in increasing inhibitory GSK3β (Ser9) phosphorylation (pGSK3β) in both CHO and SH-SY5Y cells. These agents dose-dependently increased pGSK3β, starting at 10 µM for LiCS and 60µM for LiCl and maximally by approximately 100% at 60 µM for LiCS and 1.25 mM for LiCl, without altering total GSK3β levels. In HEK293/tau cells, LiCS reduced tau (Thr231) phosphorylation (ptau) starting at 10 µM and maximally by 63% at 40 µM without altering total tau levels, but ptau levels were not altered by LiCl at any dose between 60 µM and 1.25 mM. In BV2 cells, LiCS and LiCl decreased LPS-induced TNFα levels, starting at 20 µM for LiCS and 5 mM for LiCl, and maximally by approximately 30% at 80 µM for LiCS and 20 mM for LiCl. NaCS at any dose between 5 and 90 µM did not alter pGSK3β, ptau or LPS-induced TNFα. LiCS may become a new drug with good pharmacological potential for the treatment of neurodegenerative disorders such as AD and ASD by allowing lithium to more readily access intracellular pathological processes.

B-313 Aberrant Lithium Results After HDL Assay on Roche Cobas c503 Instrument

Abstract Background Lithium is prescribed clinically to manage mania in patients with bipolar disorder. However, blood levels higher than 1.5 mmol/L (12 h post administration) indicate toxicity accompanied by severe nausea and vomiting, severe hand tremors, confusion, and vision changes. If neglected, lithium toxicity can lead to coma, brain damage, or even death. Diligent monitoring of blood lithium levels periodically is critical to preventing lithium toxicity. Case Presentation: A 37 y/o female with schizophrenia and bipolar disorder on lithium since 2019 visited the outpatient clinic for her routing biannual lithium check. The patient’s plasma lithium levels were detected at 3.9 mmol/L (previously 0.4 mmol/L; Therapeutic range: 0.60–1.20 mmol/L; Toxic: >2.00 mmol/L). The cause for elevated lithium level was unclear; EKG and vital sign were unremarkable and patient was asymptomatic for toxicity. Nevertheless, patient was then managed with IV infusions and admitted to emergency room for follow up. A redrawn lithium sample ∼22 h later was 0.3 mmol/L, suggesting no toxicity. We then investigated the discrepancy in lithium levels reported by the laboratory. Retesting of the original sample detected lithium at 0.5 mmol/L, a value significantly less than the previously reported 3.9 mmol/L. Our laboratory had recently introduced the Roche Cobas® pro integrated solutions into the lab and chemistry testing (including Lithium) are performed on the Roche Cobas c503 analyzers (an arm of the Roche pro integrated solutions). Our goal was to investigate the observed phenomenon and find potential solutions, especially as it had significant implications to patient care. Method We reviewed all high lithium levels recently tested our new instrument within a week of this incident. Seven samples (lithium values >1.2 mmol/L) were identified and lithium measurements repeated. We also investigated and ruled out the possibility of carry over contamination by rerunning a low lithium sample before and after a high lithium sample. Results Retesting all seven samples resulted in lower lithium level with an average % change of 365%. Further investigations and discussions with manufacturers alluded to interference after HDL testing on the same instrument. To investigate this hypothesis, we reran two previously reported low samples (0.3 and 0.6 mmol/L) immediately after running the HDL cholesterol assay on the Roche Cobas c503 analyzer. Retesting resulted in lithium levels of 7.32 and 1.36 mmol/L (2313.3% and 126.7% change) respectively. Conclusion Our investigation suggests that running the HDL cholesterol assay prior to the lithium assay on the Roche Cobas c503 analyzer results in positive interference. As oppose to other Roche chemistry analyzers (such as the Roche c501), the Roche Cobas c503 analyzer has no wash step between the HDL cholesterol and the lithium assays. Detergents in buffers and reactive byproducts (like peroxide) of the HDL cholesterol assay, may leave behind salts in the instrument probe that can interfere with the lithium assay. We are currently working on adding a wash step between the HDL cholesterol and lithium assays. In the interim, we are repeating lithium testing on high lithium samples.

Achieving and Maintaining Effective Plasma Concentration of Lithium After Oral Administration

The aim of the study. To study the achievability and contingency to maintain an effective plasma lithium concentration in the perioperative period in patients undergoing carotid endarterectomy (CEAE) with oral intake of lithium carbonate pills.Materials and methods. It was a prospective study, as a preparatory stage of the multicenter «BINOS» (NCT05126238) RCT. The sample included 15 patients undergoing elective CEAE. In the course of this study, patients were administered oral lithium carbonate, 900 mg per day during 4 perioperative days: two days before the procedure, in the day of surgery and in the 1st postoperative day. Plasma lithium concentration was monitored every 24 hours during all 4 days from the onset of treatment.Results. Increased plasma lithium concentrations were found in blood samples taken at 48 hours (0.68 mmol/l [0.53–0.84, P = 0.004) and 72 hours (0.68 mmol/l [0.62–0.90, P < 0.001), as compared with the initial values (0.14 mmol/l [0.11–0.17).While during the period between 48 and 72 hours from the onset of treatment the plasma lithium concentration remained in the therapeutic range (0.4–1.2 mmol/l) in 100% of patients.Conclusion. Oral intake of lithium carbonate pills at a dose of 900 mg/day during 2 preoperative days provided an effective and safe plasma lithium concentration in 100% of patients enrolled in the study.

Early Postnatal Outcome and Care after in Utero Exposure to Lithium: A Single Center Analysis of a Belgian Tertiary University Hospital.

Knowledge of the impact of in utero exposure to lithium during the postnatal period is limited. Besides a possible teratogenic effect during the first trimester, exposure during the second and third trimesters might lead to neonatal effects. Uniform guidelines for postnatal management of these neonates are lacking. The aim was to retrospectively describe all neonates admitted to the University Hospitals Leuven after in utero exposure to lithium (January 2010 to April 2020), and to propose a postnatal care protocol. Descriptive statistics were performed. For continuous parameters with serial measurements, median population values were calculated. In total, 10 mother-neonate pairs were included. The median gestational age was 37 (interquartile range, IQR, 36–39) weeks. Neonatal plasma lithium concentration at birth was 0.65 (IQR 0.56–0.83) mmol/L with a median neonate/mother ratio of 1.02 (IQR 0.87–1.08). Three neonates needed respiratory support, 7/10 started full enteral (formula) feeding on day 1. The median length of neonatal stay was 8.5 (IQR 8–12) days. One neonate developed nephrogenic diabetes insipidus. This study reported in detail the postnatal characteristics and short-term neonatal outcomes. A postnatal care protocol was proposed, to enhance the quality of care for future neonates, and to guide parental counselling. Future prospective protocol evaluation is needed.

Plus ça change? Switching lithium preparations.

A supply disruption alert in 2020, now rescinded, notified UK prescribers of the planned discontinuation of Priadel® (lithium carbonate) tablets. This service evaluation explored lithium dose and plasma levels before and after the switching of lithium brands, in order to determine the interchangeability of different brands of lithium from a pharmacokinetic perspective. Data on the treatment of 37 patients switched from Priadel® tablets were analysed. Switching to Camcolit® controlled-release tablets at the same dose did not result in meaningful differences in plasma lithium levels. Dose adjustment and known or suspected poor medication adherence were associated with greater variability in plasma lithium levels on switching brands. For comparable pre- and post-switch doses in adherent patients, the most common brands of lithium carbonate appear to produce similar plasma lithium levels. British National Formulary guidance relating to switching lithium brands may be unnecessarily complex.

Lithium administered to pregnant, lactating and neonatal rats: entry into developing brain

BackgroundLittle is known about the extent of drug entry into developing brain, when administered to pregnant and lactating women. Lithium is commonly prescribed for bipolar disorder. Here we studied transfer of lithium given to dams, into blood, brain and cerebrospinal fluid (CSF) in embryonic and postnatal animals as well as adults.MethodsLithium chloride in a clinically relevant dose (3.2 mg/kg body weight) was injected intraperitoneally into pregnant (E15–18) and lactating dams (birth-P16/17) or directly into postnatal pups (P0–P16/17). Acute treatment involved a single injection; long-term treatment involved twice daily injections for the duration of the experiment. Following terminal anaesthesia blood plasma, CSF and brains were collected. Lithium levels and brain distribution were measured using Laser Ablation Inductively Coupled Plasma-Mass Spectrometry and total lithium levels were confirmed by Inductively Coupled Plasma-Mass Spectrometry.ResultsLithium was detected in blood, CSF and brain of all fetal and postnatal pups following lithium treatment of dams. Its concentration in pups’ blood was consistently below that in maternal blood (30–35%) indicating significant protection by the placenta and breast tissue. However, much of the lithium that reached the fetus entered its brain. Levels of lithium in plasma fluctuated in different treatment groups but its concentration in CSF was stable at all ages, in agreement with known stable levels of endogenous ions in CSF. There was no significant increase of lithium transfer into CSF following application of Na+/K+ ATPase inhibitor (digoxin) in vivo, indicating that lithium transfer across choroid plexus epithelium is not likely to be via the Na+/K+ ATPase mechanism, at least early in development. Comparison with passive permeability markers suggested that in acute experiments lithium permeability was less than expected for diffusion but similar in long-term experiments at P2.ConclusionsInformation obtained on the distribution of lithium in developing brain provides a basis for studying possible deleterious effects on brain development and behaviour in offspring of mothers undergoing lithium therapy.

Treatment adherence and tolerability of immediate- and prolonged-release lithium formulations in a sample of bipolar patients: a prospective naturalistic study.

The aim of this study was to compare treatment adherence and tolerability of different lithium formulations in 70 bipolar patients receiving lithium therapy for the first time. During the 1-year follow-up, information was collected regarding patient's clinical course, therapeutic adherence, side effects of the treatment and serum levels of lithium, creatinine and thyroid-stimulating hormone. At baseline, 30 patients (43%) were on prolonged-release lithium formulations and 40 (57%) on immediate-release formulations. At the final evaluation, 37 patients (53%) were considered lost to follow-up. Both prolonged- and immediate-release patients showed significant improvement in the Functioning Assessment Short Test and in the Clinical Global Impressions for Bipolar Disorder scores during the follow-up. At the first follow-up visit, the mean plasma lithium level of prolonged-release patients was higher than immediate-release patients (0.61 vs. 0.47, respectively; P = 0.063), as well as the therapeutic adherence (85 vs. 64%, respectively; P = 0.089). Fine tremor and gastrointestinal symptoms were more frequent in immediate-release patients than in prolonged-release patients at each follow-up visit, with the sole exception of gastrointestinal symptoms at the last evaluation. Prolonged-release lithium therapy could provide potential advantages over immediate-release formulations. Future naturalistic studies and clinical trials with a longer follow-up duration are needed.

A reappraisal of the role of fever in the occurrence of neurological sequelae following lithium intoxication: a systematic review

ABSTRACT Introduction We aimed to review cases of Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) characterized by neurological sequelae following acute lithium toxicity and to explore whether cerebellar sequelae are more frequent in cases presenting with fever and/or infection. Areas covered Case reports were identified from: (i) 6 reviews published up to 2005; (ii) MEDLINE, Web of Sciences, Cochrane Library and PsycINFO search. Expert opinion We identified 123 SILENT cases published from 1965 to 2019, in which cerebellar sequelae were observed in an overwhelming proportion (79%). SILENT may occur at any time during lithium treatment. This complication is most frequently observed during routine lithium treatment, with fewer than 10% of cases occurring after accidental or intentional overdoses. SILENT may occur even when lithium plasma levels are within the therapeutic range: 63% of cases had lithium plasma level <2.5 mEq/l (low/mild toxicity). Fever and/or infection were reported in nearly half of the patients (48%). The likelihood of presenting with cerebellar vs. other neurological sequelae was independently increased by elevated plasma lithium level (≥ 2.5 mEq/l) and by a history of fever and/or infection. Lithium users should be warned of the need to consult in case of fever to adjust their lithium dosage.

Increased aluminum and lithium and decreased zinc levels in plasma is related to cognitive impairment in workers at an aluminum factory in China: A cross-sectional study

BackgroundPrevious studies have shown that multiple imbalances of metal ions in the brain are closely associated with the neurodegenerative disorders. Our studies have shown that long-term working exposure to aluminum induces increased plasma aluminum levels and causes cognitive impairment in workers at aluminum factories. ObjectiveTo explore the levels of nine metals in plasma and the effect on cognitive function among in-service workers. MethodsIn this cross-sectional study, cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), which included seven subitems: executive/visuospatial abilities; naming; attention and calculation; language; abstract; recall; and orientation. The plasma levels of nine kinds of metals were measured by inductively coupled plasma-mass spectrometry (ICP-MS). A multivariate generalized linear regression model and Bayesian kernel machine regression (BKMR) were selected to estimate the relationship between metal plasma level and MoCA scores with adjustment for confounders. ResultsOne hundred and eighty-seven workers participated in this study. In the multivariable generalized linear model, among these nine metals studied, five were related to the MoCA score: aluminum, lithium, cobalt, zinc and chromium. In the BKMR model, a significantly negative correlation between the plasma aluminum, lithium and the total MoCA score was observed. Moreover, for subitems on the MoCA scale, the plasma levels of lithium, aluminum, and zinc had a significant correlation with the executive/visuospatial abilities, naming, and orientation abilities, respectively. The log-transformation concentrations of plasma aluminum and lithium were negatively correlated with the executive/visuospatial abilities and naming abilities, respectively. The log-transformation plasma zinc concentration was positively correlated with orientation abilities. ConclusionBased on the results, we determined that increased aluminum and lithium and decreased zinc levels in plasma were associated with the incidence of mild cognitive impairment (MCI) in workers at a Chinese aluminum plant.

The effect of haemolysis on the direct and indirect ion selective electrode measurement of sodium.

We compared the effect of haemolysis in sodium measurement using indirect and direct ion-selective electrodes to test the hypothesis that haemolytic effect on sodium would be greater with indirect ion-selective electrode due to electrolyte exclusion effect from released intracellular proteins. Plasma lithium heparin samples (n = 36) from four volunteers were prepared to give a range of haemolytic indices (H-indices). Samples were analysed for sodium by indirect ion-selective electrode, H-index and total protein on an Abbott Architect c16000 and sodium by direct ion-selective electrode on a Siemens RAPIDPoint 500. Percentage changes in sodium in paired direct and indirect ion-selective electrode values were compared. Abbott H-index, which represents haemoglobin concentration in g/L, correlated with percentage negative change in sodium by direct ion-selective electrode (ρ 0.995, P < 0.001) and indirect ion-selective electrode (ρ 0.991, P < 0.001). Percentage negative change was less when sodium was measured by direct ion-selective electrode compared to indirect ion-selective electrode (Wilcoxon signed-rank Z = 3.46, P = 0.01). The difference in percentage change in sodium between direct ion-selective electrode and indirect ion-selective electrode correlated with total protein (ρ 0.751, P < 0.001). The negative bias in sodium results exceeded the reference change value of 2.2% at an H-index of 8.31 for indirect ion-selective electrode and 9.26 for direct ion-selective electrode. Haemolysis causes negative influence with sodium measured by both indirect and direct ion-selective electrode due to a dilutional hyponatremia. The additional interference in indirect ion-selective electrode is due to the electrolyte exclusion effect but this is unlikely to be clinically significant as it is small in magnitude.

Application of Lithium Assay kit LS for quantification of lithium in whole blood and urine.

A commercially available kit for the quantitation of lithium, the Lithium Assay kit LS, was originally developed to measure lithium in serum or plasma using a conventional microplate reader. We investigated whether use of the kit could be extended to quantify lithium in whole blood and urine samples collected at autopsy. The calibration curve for whole blood showed good linearity ranging from 0.5 to 20µg/mL with a coefficient of determination of 0.998 when samples were pretreated with methanol followed by acetonitrile. Moreover, for urine, we obtained excellent linearity with a coefficient of determination of 0.999 without any pretreatment. The accuracies and precisions were 106.3-174.7% and 1.9-18.1% for whole blood and 83.3-118.8% and 5.7-33.8% for urine. The values in the lower concentration range (0.5-1µg/mL) were not satisfactory, whereas those in the higher range (2-20µg/mL) were acceptable. The Lithium Assay kit LS was successfully applied to the measurement of lithium in whole blood and urine samples collected at autopsies. This method appears to be useful for forensic toxicological investigations because of its simplicity and speed.

Plasma Lithium Levels in a General Population: A Cross-Sectional Analysis of Metabolic and Dietary Correlates.

Initial evidence suggests that lithium might affect life expectancy and the risk for different disease conditions, but most studies were conducted in patients on lithium medication. Little is known about the association of blood lithium levels within the physiological range with cardiometabolic risk factors and diet. We measured plasma lithium in a community-based sample from Northern Germany (samples taken between 2010 and 2012). All participants (aged 25–82 years) underwent standardized examinations and completed a semi-quantitative food frequency questionnaire. Of several variables tested, the estimated glomerular filtration rate (eGFR) was statistically significantly (inversely) associated with lithium levels, mainly in individuals with slightly impaired renal function (eGFR < 75 mL/min/1.73 m2). Besides, lithium levels were positively associated with age and alcohol intake. Using reduced rank regression, we identified a dietary pattern explaining 8.63% variation in plasma lithium levels. Higher lithium levels were associated with higher intakes of potatoes, leafy vegetables, root vegetables, fruits, tea, beer, wine and dietetic products and lower intakes of pasta, rice, pork, chocolate, sweets, soft drinks, other alcoholic beverages, sauces and snacks. Our observations suggest that plasma lithium levels are associated inversely with kidney function, particularly in individuals with slightly impaired renal function, and positively with age and alcohol intake. Lithium at physiological levels was moderately related to an exploratory dietary pattern.

Revisiting the role of therapeutic drug monitoring in optimizing treatment outcomes in patients of bipolar affective disorders receiving lithium therapy: a prospective observational study

Background: Lithium continues to be considered first-line therapy for treatment of acute mania, acute mixed bipolar disease and long-term prophylaxis of bipolar disorder. Present study was done to study the pattern of drug therapy in bipolar affective disorder patients with special reference to lithium in the routine psychiatric outpatients care setting of a tertiary care teaching hospital as well as to understand the prospect of therapeutic drug monitoring in optimization of lithium therapy based on outcome.Methods: It was a prospective, non-randomized, observational study of a cohort of subjects who are suffering from bipolar affective disorders and on lithium therapy. Patients were prospectively followed up three monthly for three visits with therapeutic drug monitoring of their plasma lithium level, as and when advised by the treating physician, and pre-formed questionnaires.Results: Results revealed there was significant improvement in symptoms of patients who were monitored with therapeutic drug monitoring and prescribed lithium therapy in accordance with clinical pharmacological consultation for optimal dosing resulting in optimal benefit to patients.Conclusions: With regular therapeutic monitoring, optimal target serum lithium levels can be achieved with dosage modifications thereby reducing the risk of toxicity with improved drug compliance. Thus, individualization of dosing and optimization of treatment can be achieved by dependable analytical laboratory services, better psycho-education, family support and overall a disease-based management team approach with the involvement of clinical Pharmacologist to meet the complexities of lithium therapy.