When should dialysis be performed in lithium poisoning? A kinetic study in 14 cases of lithium poisoning.
ABSTRACT Lithium kinetics were studied in 14 patients with lithium poisoning. Three patients were treated by hemodialysis. Serum lithium peak concentrations ranged between 1.4 and 9.6 mmol/L. The apparent mean serum half-life was 23.16 +/- 9 h, the mean total clearance was 26.5 +/- 13.3 mL/min and the mean renal clearance was 17.2 +/- 5.4 mL/min. The kinetic parameters were dependent on the duration of the study and on the type of the poisoning: acute, acute upon chronic or chronic. During the first 12 h after admission ten patients were in a distribution phase, three were in an elimination phase and one was in an absorption phase. The serum half-life during hemodialysis ranged from 3.6 to 5.7 h and hemodialysis clearance was 63.2 to 114.4 mL/min. The mean volume of distribution calculated in six cases was 0.63 +/- 0.09 L/kg. The evolution of the lithium pools showed a different kinetic pattern between the extra- and the intracellular pool which decreased more slowly. During hemodialysis the decrease of the extracellular pool was about twice that of the cellular pool. Among the factors which may modify lithium toxicity and kinetics, are the type of the poisoning, the presence of an underlying disease and renal impairment. No general and rigid indication for hemodialysis can be set, but the need for hemodialysis should be based on clinical and kinetic data determined during the 12 h following admission.
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ABSTRACT: Lithium-induced neurotoxicity may be life-threatening. Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns. We developed acute (intraperitoneal administration of 185 mg/kg-Li2CO3 in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg-Li2CO3 in rats receiving 800 mg/l-Li2CO3 in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg-Li2CO3 during 5 days in rats with 15 mg/kg-K2Cr2O7-induced renal failure). Delayed absorption (4.03 vs. 0.31 h), increased plasma elimination (0.65 vs. 0.37 l/kg/h) and shorter half-life (1.75 vs. 2.68 h) were observed in acute-on-chronically compared to acutely poisoned rats. Erythrocyte and cerebrospinal fluid kinetics paralleled plasma kinetics in both models. Brain lithium distribution was rapid (as early as 15 min), inhomogeneous and with delayed elimination (over 78h). However, brain lithium accumulation was more marked in acute-on-chronically than acutely poisoned rats [area-under-the-curve of brain concentrations (379±41 vs. 295±26, P<0.05) and brain-to-plasma ratio (45±10 vs. 8±2, P<0.0001) at 54h]. Moreover, brain lithium distribution was increased in chronically compared to acute-on-chronically poisoned rats (brain-to-plasma ratio: 9±1 vs. 3±0, P<0.01). In conclusion, prolonged rat exposure results in brain lithium accumulation, which is more marked in the presence of renal failure. Our data suggest that differences in plasma and brain kinetics may at least partially explain the observed variability between human intoxication patterns.Toxicological Sciences 10/2014; 52(4). DOI:10.1093/toxsci/kfu224 · 4.48 Impact Factor
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ABSTRACT: For severe lithium intoxication haemodialysis is recommended to lower serum lithium levels rapidly. Frequently, serum lithium levels rebound after dialysis and repeated dialysis is needed. This is the first report of an adult patient with severe lithium intoxication who underwent haemodialysis (HD) followed by continuous veno-venous haemodiafiltration (CVVHDF). Mean lithium clearances with HD and CVVHDF were 173 and 61 ml/min, respectively. Serum lithium levels were rapidly lowered and did not rebound. Two compartment simulations illustrate that HD followed by CVVHDF is the most effective strategy for removing lithium from the intracellular compartment.European Journal of Internal Medicine 06/2009; 20(3):e70-3. DOI:10.1016/j.ejim.2008.07.013 · 2.30 Impact Factor
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ABSTRACT: Lithium is used for control of bipolar disorders. In order to precise the different circumstances at the origin of poisonings, the authors present the cases of lithium intoxication observed in the Marseille poison centre between January 1991 and December 2000. Retrospective study. Three hundred and four cases were observed during the studied period (1 patient a case), concerning 6 different circumstances. For 3 of them, the symptoms were mild: accidental ingestion with children (13 cases); mistakes on the quantities of ingested tablets (43 cases); elevation of lithium blood level due to diuretic therapy (8 cases). For 2 other circumstances, the clinical signs were more severe: treated patients who developed renal failure (15 cases, 6 patients managed in intensive care unit [ICU], 1 death) or dehydration (35 cases, 8 patients treated in ICU and 1 death). Finally, the most severe cases were collected with suicide attempts. Fifty-six percent of the patients were managed in ICU, 5% needed haemodialysis, 10% had cardiac (repolarization disturbances) or neurological (seizures) complications, 2% died. The severity of lithium poisonings depends of the circumstances. Ingestion of high quantities of sustained released tablets is the most dangerous situation. Accidental ingestion, even with children, must be considered as less severe situations.Annales Françaises d Anesthésie et de Réanimation 07/2003; 22(6):514-9. · 0.84 Impact Factor