Lithium Concentration In Blood Research Articles

Subjects suffering from bipolar disorder taking lithium are less likely to report physical pain: a FACE-BD study.

Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as a mood stabilizer, has shown promising effects on pain. This naturalistic study included 760 subjects with BD ( FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood-stabilizing blood concentration of lithium. Subjects with lithium intake were less likely to report pain (odds ratio [OR]=0.59, 95% confidence interval [CI], 0.35-0.95; p=0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5mmol/l (OR=0.45, 95% CI, 0.24-0.79; p=0.008). This is the first naturalistic study to show lithium's promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations.

Lithium Concentration in Biological Samples and Gender Difference in Athletic Horses

Lithium (Li+) represent a substance particularly used for human psychiatric disorders but its therapeutic effect is not well documented for equine specie. For its neurotrophic effect, it may be used as a possible doping substance in horses sports competitions. The purpose of the present study was to determine the different bioaccumulation of lithium concentrations in different biological substrates (blood, serum, mane, and tail), in 30 horses (15 geldings and 15 mares) and hematological parameters as blood biomarkers for lithium bioaccumulation. (RBC, WBC, HGB, HCT, MCV, MCH, MCHC). The lithium concentration in substrates were analyzed by one-way ANOVA. An unpaired t-test was performed between geldings and mares in all substrates. Furthermore, a single regression analysis (Pearson) has been carried out between the lithium concentrations of all biological substrates with each other and between the substrates with the hematological parameters. Our results showed a higher value of lithium concentration in blood and mane in total, and a higher value in mane and tail for mares than geldings. Correlation analysis showed only a significant correlation among blood, serum, and tail. A significates statistical correlation between blood and all hematological parameters except for WBC and MCH was observed. A significant correlation was shown for serum and RBC, HGB and HCT, and between tail and HGB, HCT and MCHC. No significant correlation was observed for mane and hematological parameters. These data could be useful for the evaluation of biodistribution of lithium in an athletic horse in relation to different gender for future use in doping control.

Lithium intoxication\u2013induced dysgeusia accompanied by glossalgia in a patient receiving lithium carbonate: a case report

BackgroundLithium carbonate is widely used as a first-line therapeutic agent for the depressive and manic phases of bipolar disorder. Although limb tremors and hypothyroidism are well-known side effects of lithium carbonate, other rare adverse reactions can also occur.Case presentationA 53-year-old Japanese woman diagnosed with lithium intoxication developed dysgeusia and glossalgia during treatment with lithium carbonate. She also showed symptoms of a swaying gait, finger tremors, and dysarthria. All of these symptoms subsided when her blood lithium concentration was reduced to a level below that which induces intoxication.ConclusionsWe present a rare case of lithium carbonate–induced dysgeusia accompanied by glossalgia. Early detection of these symptoms is important in clinical settings because they can be overlooked until patients lose their appetite, which severely impairs their quality of life.

Population Pharmacokinetics and Exposure-Response of Lithium Carbonate in Patients Based on Tubular Reabsorption Mechanisms.

Lithium, which is used to treat bipolar disorder, has a narrow therapeutic blood concentration range and quickly reaches clinically toxic levels. We performed a population pharmacokinetic analysis with a lithium tubular reabsorption model including urinary pH and investigated the relationship between blood lithium concentration and tremor as a side effect. Routine clinical data, including 389 serum concentrations, were collected from 214 patients orally administered an adjusted amount of lithium carbonate. Pharmacokinetics were described using a one-compartment distribution model with first-order absorption and elimination. The fractions of the MID (Li+ + LiCO3-) and ION (2Li+ + CO32-) forms were calculated using the Henderson-Hasselbalch equation, and the influences of these fractions on clearance (CL) were evaluated. The rate of tremor development was analyzed using a logit model. Oral apparent CL (CL/F) was explained by nonrenal CL and renal CL, and renal CL was varied bythe fractions of lithium forms influenced by urinary pH. The contribution of MID to CL was slightly larger than that of ION. The rate of tremor development was estimated to be more than 30% when the trough lithium concentration was greater than 1.26mEqL-1. Renal function and urinary pH are important indices in lithium treatment, so the serum concentration of lithium may be predicted based on the renal function and urinary pH.

A Method for Rapid, Reliable, and Low-Volume Measurement of Lithium in Blood for Use in Bipolar Disorder Treatment Management.

Lithium preparations are considered the most reliable mood stabilizers for patients with Bipolar Disorder (BD), and are the most effective at reducing the risk of suicide. However, maintaining blood lithium concentration within the narrow therapeutic range of 0.4-1.2 mEq is crucial but extremely difficult. The aim of this work is to develop a personal lithium blood level analyzer using a novel method of combined optical and electrical impedance spectroscopy to test micro volumes of spiked samples of human blood. Impedance measurements alone showed a limit of detection of less than 0.1mEq within the therapeutic range, whereas optical measurements could verify the presence of lithium and provide a degree of lithium content. Optical specificity to lithium was further verified in qualitative assessment of lithium spiked blood samples with varying concentrations of sodium. Moreover, analysis of multiple linear regression yielded a prediction model of R2 = 0.322716 and RMSEP = 0.223602 for optical measurements only using feature wavelengths, which were found to appear at minima 560 and 605nm. Combined with impedance measurements, prediction of lithium concentration in samples with unknown lithium content was significantly increased to R2 = 0.876438 and RMSEP = 0.513554. The combination of optical and impedance modalities for determinations of blood lithium resulted in significant improvement to the sensitivity and accuracy of measurement. Results are complementary of the proposed opto-impedance method, and future work will now focus on the technical development of an integrated and miniaturized system for measurement of lithium levels in blood with a high level of accuracy and sensitivity.

Reference values of lithium in postmortem femoral blood

IntroductionThe main recipients of lithium, people diagnosed with bipolar disorder, show an increased mortality in both natural and unnatural causes of death. Based on international data persons diagnosed with bipolar disorder comprise 2.3–9.6% of all suicidal deaths. In cases of suicide among those suffering from bipolar disorder, 17–53% are due to fatal intoxications. Diagnosing fatal intoxications is often challenging, particularly when the reference information needed to interpret the concentration of a drug is lacking or scarce. AimThe aim of this study was to establish postmortem femoral blood reference concentrations of lithium, providing both fatal and “normal” postmortem concentrations, as well as to investigate the impact of the mode of intoxication and to study the co-detection of lithium and antidepressant drugs in intoxications and controls. MethodIn Sweden, forensic autopsies are performed in unnatural and obscure deaths. This study included all autopsies in which lithium was found during the study period (1992–2010). Lithium was not included in the regular drug screen, but analysed upon request using flame photometry, ion-selective electrode detection or atomic absorption spectrophotometry. Each case was evaluated according to an established strategy, with strict inclusion and exclusion criteria followed by a multi-observer manual review (Fig. 1, Table 1). The cases included were classified as single intoxications (group A), multi-drug intoxications (group B) or controls (group C). The control group only included cases where death by intoxication and antemortem incapacitation by drugs could be ruled out. Results and discussionDuring the study period, lithium was found in 124 cases. After application of inclusion and exclusion criteria and the subsequent manual review, 21 cases were classified as group A (n=4), group B, (n=7) and group C (n=10). The femoral blood lithium concentrations in group A (median 2.69mmol/l) and group B (median 2.10mmol/l) were significantly different (p=0.01) compared to group C (median 0.2mmol/l). There were however no statistically significant difference between the concentrations in groups A and B. The most common mode of death in intoxications was acute-on-chronic (n=10), but the impact of chronic use on the fatal blood concentrations could not be evaluated since there was just one case without previous use. There was no difference in the proportion of co-detections of lithium and antidepressants between intoxication cases and controls.

Exposure to lithium through drinking water and calcium homeostasis during pregnancy: A longitudinal study

There is increasing evidence of adverse health effects due to elevated lithium exposure through drinking water but the impact on calcium homeostasis is unknown. This study aimed at elucidating if lithium exposure through drinking water during pregnancy may impair the maternal calcium homeostasis. In a population-based mother-child cohort in the Argentinean Andes (n=178), with elevated lithium concentrations in the drinking water (5–1660μg/L), blood lithium concentrations (correlating significantly with lithium in water, urine and plasma) were measured repeatedly during pregnancy by inductively coupled plasma mass spectrometry and used as exposure biomarker. Markers of calcium homeostasis included: plasma 25-hydroxyvitamin D3, serum parathyroid hormone (PTH), and calcium, phosphorus and magnesium concentrations in serum and urine. The median maternal blood lithium concentration was 25μg/L (range 1.9–145). In multivariable-adjusted mixed-effects linear regression models, blood lithium was inversely associated with 25-hydroxyvitamin D3 (−6.1nmol/L [95%CI −9.5; −2.6] for a 25μg/L increment in blood lithium). The estimate increased markedly with increasing percentiles of 25-hydroxyvitamin D3. In multivariable-adjusted mixed-effects logistic regression models, the odds ratio of having 25-hydroxyvitamin D3<30nmol/L (19% of the women) was 4.6 (95%CI 1.1; 19.3) for a 25μg/L increment in blood lithium. Blood lithium was also positively associated with serum magnesium, but not with serum calcium and PTH, and inversely associated with urinary calcium and magnesium. In conclusion, our study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results reinforce the need for better control of lithium in drinking water, including bottled water.

Exposure to Lithium and Cesium Through Drinking Water and Thyroid Function During Pregnancy: A Prospective Cohort Study.

Background: Impaired thyroid function is a common side effect of lithium medication. Recent data indicate that lithium exposure through drinking water, although providing much lower doses than the medication, may also affect thyroid hormone levels. However, the effects in susceptible groups like pregnant women are not known.Methods: In a population-based mother–child cohort in the Argentinean Andes (n = 194), an area with varying concentrations of lithium in the drinking water, we assessed lithium exposure repeatedly during pregnancy by measuring the concentrations in blood using inductively coupled plasma mass spectrometry. The markers of thyroid function included thyrotropin (TSH), free/total thyroxine (fT4/T4), free/total triiodothyronine (fT3/T3), thyroglobulin, and transthyretin in serum, sampled at the same time. Multiple potential confounders, including exposure to arsenic, cesium, and boron (elevated in water) as well as selenium and iodine (essential for thyroid function) were considered.Results: The lithium concentrations in blood [median 25 μg/L (0.0036 mmol/L); range 1.9–145 μg/L (0.000027–0.021 mmol/L)] correlated significantly with those in urine and drinking water (rs = 0.84, p < 0.001, and rs = 0.40, p < 0.001, respectively). Using linear quantile regression models, we found a positive association between blood lithium (log2 transformed) and TSH concentrations, particularly in the lowest percentiles of TSH (B = 0.20 mIU/L, [95% confidence interval 0.048–0.35] at the fifth percentile). We also found inverse associations of blood lithium with transthyretin, particularly at the highest percentiles, as well as with fT3 and T3, with less obvious variation across percentiles. Unexpectedly, blood cesium concentrations (median 111 μg/L, range 2.5–711 μg/L) were also inversely associated with fT3 and T3, particularly at the highest T3 percentiles, but not with TSH or transthyretin. Arsenic and boron exposure (also through drinking water) did not show any associations with the thyroid parameters.Conclusions: The study supports previous findings that lithium exposure through drinking water may impair thyroid function. The results regarding cesium exposure through drinking water are new. During pregnancy, impaired thyroid function may be detrimental for fetal development. The findings reinforce the need for better control of drinking water, including bottled water, as well as a health-based guideline value.

PEDAL ÖDEM: LİTYUMUN NADİR BİR YAN ETKİSİ

Lithium, is an alkali ion that is used for acute treatment and prophylaxis of mood disordes over 50 years. The most seen side effects of lithium are tremor, diarrhea, polyuria, polidipsia, hypotiroidi, weight gain, nephrogenik diabetes insipidus and nausea. Due to narrow therapeutic index, intra and interpersonal variable pharmacokinetics; close monitoring of blood lithium concentrations is recommended. Also it is suggested that lithiumneuroleptic combination can increase neurotoxicity and side effects via dopamine receptor blockade. In this case report we aimed to discuss the clinic and mechanisms of probable lithium induced pedal edema in a bipolar affective disorder patient

A prefilled, ready-to-use electrophoresis based lab-on-a-chip device for monitoring lithium in blood

We present the Medimate Multireader, the first point-of-care lab on a chip device that is based on capillary electrophoresis. It employs disposable pre-filled microfluidic chips with closed electrode reservoirs and a single sample opening. Several technological innovations allow operation with closed reservoirs, which is essential for reliable point-of-care operation. The chips are inserted into a hand-held analyzer. In the present application, the device is used to measure the lithium concentration in blood. Lithium is quantified by conductivity detection after separation from other blood ions. Measurements in patients show good accuracy and precision, and there is no difference between the results obtained by skilled and non-skilled operators. This point-of-care device shows great promise as a platform for the determination of ionic substances in diagnostics or environmental analysis.

PH-Independent Fluorescent Chemosensor for Highly Selective Lithium Ion Sensing

Since lithium salts are used as pharmaceutically active compounds against manic-depressive psychosis, there is a demand to monitor the lithium concentration in blood in the narrow range of 0.6-1.2 mM effectively and safely. Here we report on an optical sensor approach for the determination of Li+, based on the design and synthesis of a novel lithium fluoroionophore KLI-1 and its polymer immobilizable derivative KLI-2, and the application to an optode. The novel lithium fluoroionophores rely on a tetramethyl "blocking subunit" bearing 14-crown-4 as a Li+-selective binding site and 4-methylcoumarin as a fluorophore, intramolecularly connected to show ICT-type wavelength shift for ratiometric fluorescence measurements. The fluoroionophores showed high selectivity for Li+ with binding-induced blue shift in the fluorescence spectra, no response to major biological interfering cations (K+, Ca2+, Mg2+), a selectivity of log kLi+,Na+ = -2.4 over Na+ in solution, and no response to pH in the range of pH 3-10. A hydrophilic optode membrane with KLI-2 immobilized also showed good selectivity for Li+, pH independence in the physiological range (pH 6-8), and fully reversible signal changes. KLI-1 and KLI-2 are excellent Li+ fluorescent chemosensors that can be applied to quantitative measurements of lithium in clinical samples, although possible interference from Na+ has to be considered at the lower therapeutic level of Li+.

Evaluation of a new lithium colorimetric assay performed on the Dade Behring Dimension® X-pand™ system

Lithium is the standard first line of treatment for bipolar disorder. Because of its potential toxicity, levels of the drug have to be constantly monitored. To this end, an accurate and rapid assay is thus required. Moreover, lithium measurement allows differential diagnosis in patients with hallucinations, dementia and amnesia. The lithium concentration in blood is usually evaluated by flame photometry, atomic absorption spectroscopy or ion selective electrode. The aim of this study was to evaluate the analytical performance of a new colorimetric assay for lithium. Within-day precision of a pool with a target value of 1.25 mmol/l was 2.18% (CV) and day-to-day precision was assessed using serum aliquots containing two concentrations of lithium, and CVs were 5.47 and 1.6% at 0.6 and 1.15 mmol/l, respectively. The lower detection limit (LLD) was <0.08 mmol/l. The assay seemed to be linear up to 5 mmol/l. Results of a comparison method using Deming regression were: y=1.161x-0.0075 (r=0.9879) for regression with the Flame Photometer and y=0.9729 x+0.0133 (r=0.9787) for regression with atomic absorption spectroscopy. Moreover, in this study we did not find any interference with drugs or other analytes tested. In conclusion, this assay may be a method of choice for measuring lithium blood concentrations, especially in emergency situations.

Determination of lithium in food by flame photometry

Lithium has been used as a medicine for the remedy and prevention of manic-depressive psychosis. It is, however, essential to monitor the blood lithium concentration of patients during their hospital-treatments, because the intake amount of lithium as a remedy is reflected in the blood lithium concentration, which is significantly close to a toxic level. Since continual lithium intake with daily meals is expected to prevent manic-depressive psychosis at an early stage, it is important to know the food lithium content. In this work, the effects of matrix constituents (Na+, K+, Ca2+, Mg2+ and PO43−) of food on the determination of lithium by flame photometry were studied. Since there was no interference of the matrix ions, the method was applied to food samples: fresh fish (30∼84 ng/g), dry-processed fish (731 and 1790 ng/g), table-salts (667∼2340 ng/g), infant formulas (120∼160 ng/g) and eastern medicines, such as mammalian bone and oyster-shell (18700 and 20200 ng/g).

Postmortem changes in blood tranylcypromine concentration: Competing redistribution and degradation effects

Site and temporal changes in tranylcypromine (TCP) and lithium concentrations in blood were studied in a human poisoning case. Blood samples from peripheral vessels and six central vessels were obtained at 0, 6, 24, 48 and 72 h after starting the autopsy. Nine tissue samples were obtained on completion. TCP showed preferential concentration in liver (2.21 μg/g) and brainstem (2.46 μg/g). There was a moderate post mortem redistribution phenomenon with TCP concentrations lowest in peripheral blood (0.17 μg/ml) at 0 h and highest in central vessels at 24 h (0.52 μg/ml). At 72 h blood TCP concentrations fell below those at 0 time but the samples showed marked putrefactive changes. Control blood samples spiked with TCP and incubated for 48 h at 37°C showed a 58% fall in drug concentration. By contrast with TCP, lithium, which has a small Vd (0.8 l/kg) and is chemically stable, did not show this pattern of change in blood concentration. The site and temporal differences in TCP concentration in blood can be explained by the competing effects of post mortem redistribution and drug degradation. Redistribution is an early post mortem phenomenon characterised by diffusion, along a concentration gradient, from drug reservoirs in solid organs into adjacent blood vessels. Drug degradation is a later phenomenon associated with putrefactive change.

Strain dependent rate of Li + elimination associated with toxic effects of lethal doses of lithium chloride in mice

Strain differences in response to the administration of two lethal doses (700 and 900; mg/kg) of lithium chloride were studied in eight week old males from six genetic strains of mice. Two parameters were considered: (a) toxicity (time to death) and (b) hypothermia. Lithium distribution in the body (blood, seven tissues, excreta and urine) were evaluated for each strain following IP injection of 200 mg/kg dose of LiCl. The strain differences were significant for toxicity. The order of susceptibility of the strains was 129/ReJ>S.W.>C3H/S>DBA/2=Balb/c>C57/6J with a 15-fold difference between the most susceptible and the least susceptible strain at the 900 mg/kg dose. Strain differences for hypothermic response at both doses were not significant. Significant strain differences were also observed for lithium distribution in different parts of the body, excreta and urine. The concentration of Li + found in urine and excreta was positively correlated with resistance (time to death at 900 mg/kg LiCl) to the toxic effect of lithium. The lithium concentration in blood, muscle and lung on the other hand reflected a negative correlation with toxicity. The susceptibility of a strain could be characterized by its inherent lithium excretory ability, particularly through urine. It may suggest an involvement of membrane transport mechanisms in determining toxicity to lithium compounds.

Higher leukocyte nadirs with lithium carbonate after chemotherapy.

Leukocytosis has been observed following lithium carbonate administration in manic-depressive disorders (Mayfield et al.; 1966; O’Connell et al., 1970; Murphy et al., 1971). The elevation of the white blood count is modest, reversible, independent of blood lithium concentration, and due to neutrophilia (Murphy et al., 1971; Shopsin et al., 1971; Watanabe et al., 1974; Bille et al., 1975; Perez-Cruet et al., 1978, Yassa et al., 1978). Lithium may stimulate adrenocortical activity (Platman and Fieve, 1968; Shopsin and Gershon, 1971). It enhances marrow proliferation, elevates neutrophil production and increases the granulocyte pool without affecting granulocyte function or inhibiting neutrophil migration into skin lesions (Tisman et al., 1973; Rossof and Coltman, 1976; Malloy et al., 1978; Rothstein et al., 1978; Shenkman et al., 1978; Stein et al., 1978; Cohen et al., 1979; Steinherz and Smithwick, 1979). The mechanism by which lithium exerts its effect in vivo is unclear; however, it stimulates the formation of granulocytic colonies in the agar culture system either by stimulating the synthesis of colony stimulating factor (Harker et al., 1977) or by enhancing the action of colony stimulating factor (Morley and Galbraith, 1978). Increase in leukocyte numbers has also been observed with lithium treatment in patients with neutropenia secondary to Felty’s syndrome or aplastic anemia, and in congenital and acquired neutropenia (Gupta et al., 1975; Gupta et al., 1976; Barrett et al., 1977; Blum et al., 1979; Chan et al., 1979; deAlarcon et al., 1979). Reports of improved counts after cancer chemotherapy in small trials (Tisman, 1974; Greco and Brereton, 1977; Charron et al., 1977; Catane et al., 1977; Stein et al., 1977; Tiefenbach et al., 1977; Steinherz et al., 1979a) prompted us to evaluate lithium carbonate after chemotherapy in a randomized, paired, prospective study (Steinherz et al., 1979b.).KeywordsAplastic AnemiaLithium TreatmentWhite Blood CountPlasma Cortisol ResponseInhibit Neutrophil MigrationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Studies on the use of blood lithium concentrations in lithium therapy in Japan.

The relationship between the concentration of lithium in whole blood and plasma was determined in 11 manic-depressive patients 12 h after the evening dose of lithium carbonate taken in the form of slow release tablets (Limas). Significant relationships were found between the concentration of lithium in whole blood and plasma as well as between the daily dose of lithium and the lithium concentration in whole blood and in plasma. The findings suggest that under certain conditions the concentration of lithium in a small sample of whole blood may be used to monitor lithium therapy in outpatients. The advantages of using whole blood are discussed.

Lithium chloride and dilithium carbamyl phosphate: Lithium distribution and toxicity in mice

Dilithium carbamyl phosphate, an antisickling agent, dissociates into lithium cations and carbamyl phosphate dianions in solution. In order to determine which ion is primarily responsible for the toxicity observed at very high doses of dilithium carbamyl phosphate, two groups of 15 mice each were given similar amounts of lithium in twice-daily ip injections for 21, 23, or 30 days. Six of the fifteen mice survived in group A (lithium chloride, 12.9 mEq of Li +/kg/day), and 8 of 15 mice survived in group B (dilithium carbamyl phosphate, 13.8 mEq of Li +/kg/day). Blood lithium concentrations measured 4–6 hr after an injection averaged 1.7 (±0.7 SD) mEq/liter for each group. Lithium concentrations were measured in 39 samples of tissue or tissue contents from mice in each group. In the surviving animals, lithium ranged from an average of 0.8 – 1.1 mEq/kg in liver to 5–15 mEq/kg in the contents of the lower intestinal tract. Lithium concentrations greater than 15 mEq/kg were often found in the tissues of the nonsurvivors. Hemoglobin carbamylation was 1.0 (±0.3 SD) mol of valine hydantoin/mol of hemoglobin tetramer in mice given dilithium carbamyl phosphate for 21–30 days. This study demonstrates that the toxic effects associated with administration of dilithium carbamyl phosphate appear to be due to the lithium cation rather than the carbamyl phosphate dianion. In all parameters measured, the toxic effects of lithium chloride paralleled those observed when an equivalent amount of lithium was administered as dilithium carbamyl phosphate.