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.

Effect of fasting on serum lithium levels: an experimental study in animal models

Muslims throughout the world observe dawn to dusk fast in the month of Holy Ramadan. This study aims to investigate the effect of fasting on serum lithium levels in an animal model under typical conditions of Ramadan. Animals were categorized into oral and intraperitoneal groups. Each group was divided into fasting and non fasting groups along with their controls having six animals each. Mean serum lithium levels of non-fasting and fasting rats were assessed. Mean serum lithium levels of oral non-fasting rats was 0.23 +/- 0.004 mequiv/L, [n=6] compared to oral fasting rats 0.20 +/- 0.002 mequiv/L, [n=6] mean difference=0.003. The mean difference between mean serum lithium level of intraperitoneal non fasting [0.246 +/- 0.015 mequiv/L, n = 6] and intraperitoneal fasting rats [0.206 +/- 0.020 mequiv/L, n = 6] was 0.02. These differences were statistically non significant [P>0.05]. The mean serum lithium is not grossly affected by fasting in rats under 25degreeC and fasting for almost 12 hours which is consistent with a previous clinical study. Lithium can be used by fasting bipolar patients but, will require careful supervision.

Lithium-induced sinus node dysfunction at therapeutic serum levels.

Lithium-induced cardiotoxicity, though rare at therapeutic levels, has been reported frequently in overdoses. We report a patient who developed sinus bradycardia while being treated with lithium carbonate even though the serum lithium levels were within the therapeutic range. It reversed following withdrawal of lithium and did not reappear with subsequent treatment with valproate.

Evaluation of lithium genotoxicity

This study was conducted on twenty patients having manic-depressive psychosis and treated by lithium for a period from 1-5 years. Determination of serum lithium level was done to all patients [n=20] using flame photometer. Heparinized venous blood [5ml] was withdrawn from every patient. The following genotoxic assays were performed; assay of sister chromatid exchanges [SCEs] frequencies in cultured human leucocytes and in vivo -in vitro analysis of human karyotype. The genotoxic assays performed on mice included micronucleus test [MNT] and analysis of chromosomal aberrations in mice bone-marrow cells. The present study showed that serum lithium level ranged from 0.37 to 1.07 mEq/L with a mean of 0.77 +/- 0.18 mEq/L. The study revealed a statistically insignificant increase in the frequencies of SCEs in cultured human leucocytes, while a significant in crease of structural chromosomal aberrations was observed in the form of sticky chromosomes, eroded chromosomes, acentric and deletions. In mice, lithium carbonate has a weak clastogenic effect upon mice chromosomes when used in a therapeutic dose, but it has a definite clastogenic effect when administered in a dose more than the therapeutic dose as demonstrated by the significant increase in micronucleated polychromatic erythrocytes and structural chromosomal aberrations. The present study proved the clastogenic potentiality of lithium carbonate

Efeitos da intoxicação por lítio sobre a locomoção de ratos em um modelo animal de insuficiência renal aguda cirurgicamente induzido / Effects of lithium toxicity on rat locomotion in an animal model of surgical induced acute of kidney failure

INTRODUÇÃO: O lítio é um metal usado sob a forma de sal para tratamento de episódios agudos de mania e no controle profilático de desordens afetivas bipolares. Pacientes com algum grau de insuficiência renal podem rapidamente sofrer intoxicação por esse fármaco. Nosso objetivo foi verificar a influência da litemia na locomoção em um modelo animal cirurgicamente induzido de insuficiência renal aguda (IRA). MÉTODOS: Foram submetidos 61 ratos Wistar a tratamento com lítio por uma semana previamente a nefrectomia unilateral. Trinta ratos foram induzidos a IRA. Foi administrado lítio ou solução fisiológica aos ratos e após observada sua locomoção e concentração de creatinina sérica. Utilizou-se análise estatítica. RESULTADOS: A creatina apresentou-se elevada nos ratos com IRA. A locomoção foi menor nos ratos com IRA que receberam lítio, havendo relação inversa entre a litemia e a atividade locomotora. CONCLUSÕES: O modelo animal cirúrgico de IRA foi efetivo. Ratos insuficientes renais que receberam lítio apresentaram alterações locomotoras comparados aos demais. O aumento da litemia causa diminuição proporcional na locomoção dos ratos.

Tratamiento de la enfermedad bipolar durante el embarazo y puerperio: caso clínico / Treatment of a pregnant patient with a bipolar disorder: clinical case

We report a 37 years old woman with a severe bipolar disorder, that became pregnant during treatment with lithium. The patient and her family were informed about the 0.05-0.1 percent risk of cardiac malformations of the newborn, but decided to maintain her pregnancy and not to discontinue the use of lithium, fearing a relapse of her psychiatric ailment. She continued under medical surveillance and had a normal delivery, but no breast feeding was allowed

Lithium clearance and sodium lithium counter transport in insulin dependent diabetes mellitus

Our study was conducted on 24 insulin dependent diabetic patients in comparison to 10 normal healthy control subjects. the group of the patients were classified according to the results obtained into 3 groups. The list was eight diabetic patients without nephropathy, the second was eight diabetic patients with nephropathy and the third was eight diabetic hypertensive patients, Both diabetics and control were subjected to full clinical examination and laboratory investigations [plasma lithium, lithium clearance, fractional Iithium clearance [FcLi] and sodium-lithium counter transport [Na [+] /Li [+] CT]. The results showed mild elevation of serum sodium in IDDM groups compared to control. FcLi showed a highly reduction in IDDM groups compared to control group. Na [+] /Li [+] CT showed a statistically significant elevation in IDDM groups compared to control group

Lithium neurotoxicity at therapeutic level--a case report.

A 30 years old Hindu male presenting with symptoms of lithium toxicity. On investigation, serum lithium level was found to be 0.5 meq/l. Though toxicity at this level of lithium is unusual, still neurotoxicity happened to be the cause of his hospital admission. He was debarred from taking lithium further and carbamazepine was started as mood elevator. He responded favourably.

Dosagem de Lítio: Alerta / Lithium; Lithium`s serum level

A partir da observaçäo de incoerências entre dados clínicos e resultados laboratoriais, os autores formularam a hipótese de que a mensuraçäo sérica de Lítio pode näo ser confiável em pelo menos alguns laboratórios. Coletaram-se amostras de sangue de dez pacientes internados portadores de distúrbio bipolar e em tratamento com carbonato de Lítio. Foram realizadas dosagens séricas de Lítio de cada amostra em cinco laboratórios. Encontraram-se discrepâncias significativas entre os resultados das dosagens. Os resultados sugerem que as dosagens séricas de Lítio em pelo menos alguns laboratórios estäo sujeitas a variaçöes clínicamente significativas. Recomenda-se a realizaçäo de estudos mais abrangentes para se avaliar a extensäo do problema

Study of the effect of lithium on plasma glucose, insulin and glycogen in normal and streptozotocin induced diabetic rats

Lithium [Li] is used widely in different psychiatric disorders. It has variable and inconclusive effects on glucose tolerance. The objective of the study was to examine the effects of lithium on plasma glucose [G], glucagon and insulin, and their responses to IV G in male wistar rats. Plasma G, glucagon [by RIA], insulin [by RIA], and serum Li [by flame photometry] were measured before and 30 min after IV Li chloride [4 mEq/kg] in 10 normal and 10 streptozotocin induced diabetic rats [under light ether anaesthesia]. These parameters were also determined before, at 30 and 90 min following combined IV administration of Li chloride [4 mEq/kg] and G [0.5 g/kg] in 10 normal and 10 diabetic rats. In normal rats, Li injection resulted in a significant increase in mean plasma G [55%] and glucagon [91%]. This was associated with a significant drop in mean plasma insulin [71%]. Combined Li and G administration was followed by an increase in both mean plasma G [42%] and glucagon [98%]; a further elevation was observed at 90 min. The addition of G to Li failed to alter the inhibitory effect of the latter on plasma insulin which persisted till 90 min.. In diabetic rats, mean fasting plasma G and glucagon were significantly higher than those in normal rats, while mean plasma insulin was significantly lower [p < 0.001]. Administration of Li was associated with a further significant increase in plasma G and glucagon and a decrease in plasma insulin. Addition of G to Li failed to alter the responses of mean plasma G, glucagon and insulin, when compared to Li alone. These changes did not persist at 90 min as in normal rats. Serum Li levels [basal and after Li injection] were comparable in normal and diabetic rats. We conclude that acute Li administration is associated with an increase in plasma glucose in both normal and diabetic rats. This hyperglycemia is due to accelerated glucagon and diminished insulin secretion

Reduced renal sodium excretion in walker-256 tumor-bearing rats

Subcutaneous inoculation of Walker-256 tumor is followes by an asymptomatic period which is widely variable in duration, after which, paraneoplastic effects appear suddenly in the form of progressive and rapidy changing homeostatic alterations. Multifocal inoculation of tumor cells in each animal, was carried out with data averaging in each (sub-clinical [SubC], moderate [mCP] and grave [gCP] clinical phases and compared to foodrestrieted FR. The renal sites involved were studied in awake unrestrained animals by measure of sodium, cratinine and lithium clearance. Results indicated an initial increase of both absolute proximal (mCP:21.4+1.7 vs FR: 16.0+1.1 mmol/min/100 g.b.w., p<0.05) and postproximal (mCP:11.1+0.4 vs FR:6.6+0.4 mmol/min/100g g.b.w., p<0.001) Na+ reabsorption, which were partially compensated by a rise in glomerular filtration rate (mCP:213+11.4 vs FR: 162+10.2p1/min/100 g.b.w., p<0.01) and by fell of fractional proximal Na+ reabsorption (mCP:62.8+ vs FR: 70.1+1.7 per cent, p<0.05), despite this a significant Na+ and fluid retention was observed. Additionally, this study shows that terminal phase of the illness (gCP) culminated with a marked decrease in the creatinine clearance suggesting a significant fall of the renal function.

Chronic but not acute Li+ treatment prevents behavioral depression in rats

The effect of lithium administration on the learned hellessness model of depression was investigated. Female Wistar rats (190-210g) received either tap water alone (N=156) or 20 mM LiCL, provided chronically (30 days; N = 127) or acutely (5 days; N = 22), in the drinking water. Three days before the end od treatment, each group was divided into two subgroups which received either inescapable shock (IS) or no shock (NS) treatment in shuttle boxes. All groups were subsequenty submitted to an escape test on the following day and then sacrificed one day after the escape test, when blood samples were taken to measure serum Li+, Na+ and K+ concentrations by flame photometry. There were no significant differences in serum Na+ amongst the 4 groups. chronically treated NS and IS rats both presented an increase in serum K+ compared to the control rats. The IS and not the NS chronically treated rats presented increased serum Li+ levels which cannot be accounted for in terms of differences in Li+ intake. The IS group treated chronically with lithium had a better escape performance than the IS group receiving either tap water or acute Li+ administration. We conclude that chronic but not acute Li+ treatment at a serum level within the prophylactic range (0,5 mEq) is able to prevent learned helplessness in the rat. These results agree with the data obtained in clinical practice indicating that li+ is only effective after chronic administration and that Li+ - induced hyperkalemia is a side effect

Developmental toxicity of lithium treatment at prophylactic levels

Lithium (Li+) salts are frequently used in psychiatry and may be administered to women in theirreproductive years. We have investigated the influence of chronic Li+ administration on rat offspring. Pregnant Wistar rats drank either tap water ad libitum or 10 mM LiCl, or were water restricted (paired to rats receiving LiCl) until pup weaning. Following birth, pups were fostered to form five experimetnal groups (N = numbers of litters): a) Control-S, stressed by water restriction (N = 21), b) Li+ during the prenatal and lactating periods (N=18),c) Li+ during the prenatal period only (N=22), d) Li+ during the lactating period only (N = 15), and e) Control-NS no treatment (N = 13). Prenatal water restriction of Li+ treatment impaired the performance of the righting reflex, altered the number of males born and delayed the final date of eye opening. Postnatal water restriction or Li+ treatment of the dams reduced body growth and the date of eye opening of pups. No difference was found in the time to pup earflap opening, or in the motor coordination test. The specific effect of lithium on pups included impairment of the righting reflex, an increase in the number of males born, a reduction in body weight at weaning and a delay in the eye opening date. The serum Li+ levels of the dams were maintained at approximately 0.5 mEq/l. Ther was an increase in serum potassium, but not sodium, concentrations. We conclude that chronic treatment of dams with Li+ in amounts similar to those used in the prophylaxis of bipolar disorders aggravated the delay in physical and behavioral development of pups produced by stress associated with limited water intake and handling

Dosagem de lítio em nosso meio: um alerta! / Levels of serum lithium amid us: an alert!

A partir de dados da observaçäo clínica, os autores formularama hipótese de que as dosagens séricas de lítio em seu meio säo pouco confiáveis. Pacientes e métodos: seis pacientes portadores de distúrbio bipolar e em tratamento de manutençäo com carbonato de lítio fizeram dosagens séricas de lítio em três laboratórios. Resultados: foram encontradas grandes variaçÆes nos resultados dos laboratórios. ConclusÆes: apesar das limitaçÆes metodológicas, os resultados encorajaram uma avaliaçäo mais profunda e extensa do problema em nosso meio

Serum zinc, lithium and thyroid hormones in patients with chronic renal failure

The association of changes in serum trace elements [zinc and lithium] with thyroid hormones [thyroxine and triiodothyronine] in patients with established renal failure studied. Thirty patients of both sexes with established renal failure of divert causes and subjected to renal dialysis were enrolled in this study. Renal dialysis increases the level of thyroid hormones but did not alter the status of serum zinc and lithium. Serum thyoid hormones were correlated positively with serum zinc and negatively with serum lithium. This pattern of correlation was not altered by renal dialysis. It could be concluded that certain trace elements are playing a role in the regulation of thyroid function particularly in diseases other than thyroid

Study of red cell sodium-lithium counter transport activity in diabetic nephropathy

Few controversial studies have been reported about red cell Sodium-lithium counter transport [SLC] in patients with essential hypertension and diabetes mellitus. To relate red cell SLC to essential hypertension and diabetes with or without nephropathy, we studied SLC activity [mmol/liter of red cells/hour] in 10 non-diabetic hypertensive patients and 30 diabetics [10 non- hypertensive without clinical nephropathy and 10 hypertensive with clinical nephropathy] compared with 10 healthy controls. Non-diabetic hypertensive and non- hypertensive diabetics had insignificantly higher levels of SLC activity compared with controls [0.336 +/- 0.02 and 0.366 +/- 0.02 vs 0.273 +/- 0.26, respectively]. Non- hypertensive nephropathic diabetics had a significantly SLC [0.466 +/- 0.3] compared with controls [P<0.001]. non-diabetic hypertensive. [P< 0.01] and non-nephropathic non- hypertensive diabetics [P< 0.05]. following the same order subjects with SLC activity>0.4 were 90%, 0%, 10% and 20%. All hypertensive diabetics with nephropathy had SLC activity>0.4 [100%] with a significantly higher value compared with other groups [P< 0.001]. We conclude that elevated red cell SLC activity can be considered as a useful screening test to detect a subset of diabetics in whom all preventive modalities against development of nephropathy should be energetically applied

Reversal of learned helplessness by chronic lithium treatment at a prophylactic level

1. The effect of chronic lithium (Li) administration in a learned helplessness (LH) model was investigated. Female Wistar rats (190-210 g) received either tap water ad libitum (N = 56) or 20 mM LiCl (N = 63) in the drinking water or were water restricted (35 per cent based on lower liquid intake of rats receiving lithium, N = 40) for 30 days. On the 28th day, each of these groups was divided into three subgroups which received escapable (ES), inescapable (IS) or no shock (NS) treatment in shuttle boxes. All groups were submitted to the escape test on the 29th day and sacrificed on the 30th day, when blood samples were taken for measurement of serum lithium, sodium and potassium concentrations. 2. The NS group had lower serum Li levels (0.36 +/- 0.06, N = 15) than the ES (0.46 +/- 0.07, N = 15) or IS group (0.44 +/- 0.09, N = 25). The Li-pretreated group subjected to IS had a more effective escape performance than the IS group under water restriction and showed the same behaviour as animals not submitted to shocks. 3. We conclude that chronic treatment with Li at a serum level of 0.44 +/- 0.09 mEq/l prevents learned helplessness in rats. These results corroborate the validity of the use of this model for the assessment of the capacity of Li to protect against some depressive episodes

Predictors of lithium therapeutic response in mania

Fourty patients diagnosed as Mania according to the criteria of ICD-10 were subjected to full Clinical psychiatric examination and psychometric assessment using Manic Rating Scale and Scale for Affective Disorder [SAD] derived from schedule for affective disorder and schizophrenia [SADS]. Investigations were done at the Start of lithium therapy and every week for one month, the dose of lithium was adjusted according to plasma level using flame emission photometer positive family history of affective .disorders was found to predict good outcome, while older age, previous depression, younger age of onset, paranoid features and formal thought disorders were found to predict poor outcome