Serum fluoride

Fluoride taken in the form of sodium fluoride as a tablet or solution is absorbed rapidly. Only a few minutes after intake, there is a rise in plasma fluoride. The fluctuation in plasma fluoride concentration is dependent on the fluoride dose ingested, the dose frequency and the plasma half-life of fluoride. The half time for absorption is --30 min, so peak plasma concentration usually occurs within 30-60 min [64-69]. Absorbed fluoride is rapidly distributed by the circulation to the intracellular and extracellular fluids and is retained only in calcified tissues. The sensitivity of the serum fluoride concentrations to previous intake, glomerular filtration and the intensity of bone resorption suggests that the human organism exerts no direct homeostatic control and that fluoride concentrations reflect the recent intake [73]. Plasma fluoride levels increase with age, with increasing fluoride content of bone and as a consequence of renal insufficiency [2]. 

Fluoride readily crosses the placenta and is found in foetal and placental tissue. There appears to be a direct relationship between fluoride levels in maternal blood and cord blood [79-82]. At relatively low maternal blood levels, the cord blood levels were at least 60% of that of maternal blood [80,82]. Although cord fluoride levels were typically lower than maternal levels, one study found no statistical difference between maternal and newborn (1-day-old) serum fluoride levels, suggesting that cord serum fluoride levels do not reflect foetal fluoride status [83]. There is also evidence, however, that the placenta can accumulate fluoride, possibly playing a regulative role that helps protect the foetus from excessive amounts of fluoride, when maternal fluoride intake is high [79,84]. 

The accepted therapeutic range of the serum fluoride levels has been suggested to be 5-10 pmol L-1 and the therapeutic window 95-100 pg L-1 (5 pmol L-1) is not assumed to be overtly cytotoxic [92]. 

Elevated aluminum levels have been implicated as the cause of dialysis encephalopathy or dementia in renal failure patients undergoing long-term hemodialysis [85]. Some patients used aluminum-containing medications. Moreover, patients with renal failure cannot remove aluminum from the blood. Dialysis dementia can arise after three to seven years of hemodialysis treatment. Speech disorders precede dementia and convulsions. Since many hemodialysis units rely on systems to purify fluoridated tap water, it is likely that many patients are being exposed inadvertently to increased concentrations of fluoride and aluminum. Increased serum fluoride concentration and fluoride intoxication have been also observed in chronic hemodialysis patients. Arnow et al. [96] reported that 12 of 15 patients receiving dialysis treatment in one room became acutely ill, with multiple non-specific symptoms and fatal ventricular fibrillation. Death was associated with longer hemodialysis time and increased age compared with other patients who became ill. 

A mean peak serum-fluoride concentration of 0.2 ig/ml was attained 3 hours after induction in 18 subjects receiving 0.6 to 2% v/v of enflurane (P. Duvaldestiner fl/., Clin. Pharmac. Ther., 1981, 29, 61-64). 

Conzen PF, Nuscheler M, Melotte A, Verhaegen M, Leupolt T, Van Aken H, Peter K. Renal function and serum fluoride concentrations in patients with stable renal insufficiency after anesthesia with sevoflurane or enflurane. Anesth Analg 1995 81(3) 569-75. 

Nephrotoxicity has been found with methoxyflurane when serum fluoride ion concentrations exceeded 50 pmol/l (SEDA-20,106). Although this safety threshold has been applied to other volatile anesthetics as well, renal toxicity has not been reported for the other three anesthetics, even though the threshold can be exceeded during prolonged anesthesia. 

A 29-year-old mau was auesthetized after reual traus-plantatiou with sevofluraue + uitrous oxide + oxygen for replacement of the head of the left femur (57). His serum fluoride couceutratiou was always below 40 pmol/l and sevoflurane had little effect on the transplanted kidney. 

Symptoms Gastric symptoms nausea, salivation, abdominal pain Direct effects of fluoride Inhibition of metabolism Persistent abnormal serum fluoride levels... 

Consistent with its blood gas partition coefficient, induction of anesthesia and recovery from enflurane are relatively slow (Table 13-1). Enflurane is metabolized to a modest extent (2-8% of absorbed enflurane) by hepatic CYP2E1. Fluoride ions are a by-product of enflurane metabolisrrr but plasma fluoride levels are low and nontoxic. Patients taking isoniazid exhibit enhanced metabolism of enflurane with a consequent elevation of serum fluoride. 

A. Specific levels. The normal semm fluoride concentration is less than 20 mcg/L (ng/mL) but varies considerably with diet and water source. Serum fluoride concentrations are generally difficult to obtain and thus are of limited utility for acute overdose management. 

A 46-year-old woman underwent anaesthesia for renal transplantation 6 days after starting isoniazid 300 mg daily. Anaesthesia was indueed with intravenous thiopental and maintained for 4 hours with 60% nitrous oxide, fentanyl and isoflurane. Serum fluoride ions inereased from 4.3 mieromol preoperatively to approximately 30 mieromol between 2 and 8 hours after starting isoflurane. However, no impairment of renal funetion occurred. A second patient who was given 5 times the first patient s exposure to isoflurane and who had received isoniazid for 13 years showed no increase in serum fluoride concentrations over preoperative values, but did show an increase in trifluoroacetic acid levels. ... 

Fluoride, on the other hand, is a trace element in animals and is normally present in blood serum at about the 5 X 10 mol dm level, but this can be considerably enhanced in patients anaesthetised with certain fluorocarbons and in the employees of certain important industries. The recent interest in fluoridation of water supplies has also focused attention on serum fluoride, but a dif-Hculty here is access to low fluoride serum for preparing standards. Hence, human serum from a normal young adult who has not drunk fluoridated water for 24 h is acceptable when the inorganic fluoride will be <5 XIO mol dm" [160] fluoride-free water may also be used with little loss of accuracy. 

In an investigation of the movement of fluoride in haemodialysis it has been shown [175] that when the dialysate is prepared with fluoridated water, fluoride moves from the dialysate to blood at a rate comparable with the movement of solutes in the opposite direction. It is suggested that the resulting serum fluoride values are likely to result in altered bone formation [175]. 

Liver biopsies showed moderate to severe fatty infiltration, thereby possibly increasing uptake of methoxyflurane and exposed more methoxyflurane to hepatic microsomal enzymes [208]. Control halothane-nitrous oxide anaesthesia with 12 obese patients led to a peaking in the serum fluoride level after 3 h anaesthesia (10.4 1.5 /tmol dm" ) [208]. 

A separate study with patients anaesthetised without nitrous oxide supplementation gave peak serum fluoride values of 190.4 20.9 jumol dm , probably owing to the higher dose of methoxyflurane [218]. 

Methoxyflurane anesthesia may determine elevated serum inorganic fluoride levels and polyuric renal failure (serum fluoride levels >50 pmol/dl were associated with an increased risk of renal damage) [49]. 

Linear regression and correlation analysis indicated highly significant relationship between serum fluoride with TC HDL, triglycerides and TC/HDL ratio in fluorotic patients exposed to different levels of fluoride. This shows that fluoride may cause distmbances in lipid metabolism. The decline in the cholesterol content may be due to inhibition of lipid synthesis by fluoride as well as an increase in utilisation of stored lipids as a source of energy to conduct regular metabolic functions. 

---