Serum Inorganic Fluoride Levels Research Articles

Renal safety of critical care sedation with sevoflurane: a systematic review and meta-analysis.

Volatile anesthetic agents are increasingly widely used for critical care sedation. There are concerns that sevoflurane presents a risk of renal injury when used in this role. RCTs comparing the use of critical care sevoflurane sedation with any control in humans were systematically identified using MEDLINE, Cochrane CENTRAL, web of Science, and CINAHL (until May 2022), if they presented comparative data on renal function or serum inorganic fluoride levels. Pooled SMDs (95% CI) were calculated where possible after assessment of quality with GRADE and risk of bias with ROB-2. Eight studies analyzing 793 patients were included. The median duration of use of critical care sevoflurane sedation was 4.8 [IQR 3.5-9.2] hours; however, most trials also included a period of prior intraoperative use. No significant difference was found in serum creatinine at 1day (SMD 0.05, 95% CI - 0.12 to 0.21), 48h (SMD = - 0.04; 95% Cl - 0.25 to 0.17), 72h (SMD = - 0.15; 95% CI - 0.45 to 0.15), and at discharge (SMD = - 0.1; 95% CI - 0.3 to 0.13) between the sevoflurane group and the control groups. Creatinine clearance was measured in two studies at 48h with no significant difference (SMD = - 0.13; 95% Cl - 0.38 to 0.11). Levels of serum inorganic fluoride were significantly elevated in patients where sevoflurane was used. Sevoflurane was not associated with renal failure when used for critical care sedation of fewer than 72-h duration, despite the elevation of serum fluoride. Longer-term studies are currently inadequate, including in patients with compromised renal function, to further evaluate the role of sevoflurane in this setting.Trial registration PROSPERO (CRD42022333099).

The Effects of Sevoflurane Anesthesia and Cardiopulmonary Bypass on Renal Function in Cyanotic and Acyanotic Children Undergoing Cardiac Surgery

Background: There are few data on the effects of anesthesia and cardiopulmonary bypass (CPB) on perioperative renal function in children with cyanotic congenital heart disease undergoing open heart surgery. This study aims to investigate the perioperative renal function in cyanotic versus acyanotic children undergoing sevoflurane anesthesia for open heart surgery. Methods: After receiving ethical committee approval, 12 acyanotic patients (preoperative oxygen saturation: SaO2 > 85%) and 12 cyanotic children (SaO2 < 85%) were included. Sevoflurane was administered at concentration levels of 2% before CPB and 1–2% during CPB after standard anesthesia induction. Inorganic fluoride, electrolytes, creatinine, urea nitrogen in serum and urine samples, and N-acetyl-β-d-glucosaminidase (NAG) in urine samples were measured before induction, before CPB, during CPB, after CPB, at the end of surgery, and at 24th h postoperatively. Results: The levels of serum uric acid levels were higher in the cyanotic group (p < 0.05). There were no differences in the levels of serum creatinine and urine creatinine, urea nitrogen, and electrolytes between the two groups. Serum inorganic fluoride levels were always higher in the acyanotic group than in the cyanotic group, but these differences between the groups reached statistical significance at two measurement times (before CPB and end of surgery) (p < 0.05). Urinary inorganic fluoride levels increased with time in both groups. Although urinary NAG increased significantly after the CPB in the cyanotic group, the differences between the two groups did not reach statistical significance. Conclusions: We have concluded that renal function was not affected during open heart surgery with sevoflurane anesthesia, in both cyanotic and acyanotic children.

Methoxyflurane Revisited

Methoxyflurane metabolism and renal dysfunction: clinical correlation in man. By Richard I. Mazze, James R. Trudell, and Michael J. Cousins. Anesthesiology 1971; 35:247-52. Reprinted with permission. Serum inorganic fluoride concentration and urinary inorganic fluoride excretion were found to be markedly elevated in ten patients previously shown to have methoxyflurane induced renal dysfunction. Five patients with clinically evident renal dysfunction had a mean peak serum inorganic fluoride level (190 +/- 21 microm) significantly higher (P < 0.02) than that of those with abnormalities in laboratory tests only (106 +/- 17 microm). Similarly, patients with clinically evident renal dysfunction had a mean peak oxalic acid excretion (286 +/- 39 mg/24 h) significantly greater (P < 0.05) than that of those with laboratory abnormalities only (130 +/- 51 mg/24 h). That patients anesthetized with halothane had insignificant changes in serum inorganic fluoride concentration and oxalic acid excretion indicates that these substances are products of methoxyflurane metabolism. A proposed metabolic pathway to support this hypothesis is presented, as well as evidence to suggest that inorganic fluoride is the substance responsible for methoxyflurane renal dysfunction.

A phase III, multicenter, open-label, randomized, comparative study evaluating the effect of sevoflurane versus isoflurane on the maintenance of anesthesia in adult ASA class I, II, and III inpatients

Study Objective: To compare the clinical efficacy and safety of sevoflurane and isoflurane when used for the maintenance of anesthesia in adult ASA I, II, and III inpatients undergoing surgical procedures of at least 1 hour's duration. Design: Phase III, randomized, open-label clinical trial. Setting: 12 international surgical units. Patients: 555 consenting inpatients undergoing surgeries of intermediate duration. Interventions: Subjects received either sevoflurane (n = 272) or isoflurane (n = 283) as their primary anesthetic drug, each administered in nitrous oxide (N 2O) (up to 70%) and oxygen (O 2) after an intravenous induction using thiopental and low-dose fentanyl. The concentration of volatile drug was kept relatively constant but some titration in response to clinical variables was permitted. Comparison of efficacy was based on observations made of the rapidity and ease of recovery from anesthesia and the frequency of untoward effects for the duration of anesthesia to the return of orientation. Safety was evaluated by monitoring adverse experiences, hematologic and non-laboratory testing, and physical assessments. In 25% of patients (all patients in both treatment groups at selected investigational sites), plasma inorganic fluoride concentrations were determined preoperatively, every 2 hours during maintenance, at the end of anesthesia, and at 1, 2, 4, 8, 12, 24, 48, and 72 hours postoperatively. Measurements and Main Results: Emergence, response to commands, orientation, and the first request for postoperative analgesia were all more rapid following discontinuation of sevoflurane than following discontinuation of isoflurane (sevoflurane, 11.0 ± 0.6, 12.8 ±0.7, 17.2 ± 0.9, 46.1 ± 3.0 minutes, respectively, versus isoflurane, 16.4 ± 0.6, 18.4 ± 0.7, 24.7 ± 0.9, 55.4 ± 3.2 minutes). The incidence of adverse experiences was similar for sevoflurane and isoflurane patients. Forty-eight percent of patients in the sevoflurane group had no untoward effects versus 39% in the isoflurane group. Three patients who received sevoflurane had serum inorganic fluoride levels 50 μM/L or greater though standard tests indicated no evidence of associated renal dysfunction. Conclusion: Sevoflurane anesthesia, as compared with isoflurane, may be advantageous in providing a smoother clinical course with a more rapid recovery.

Correlation Between Renal Function and Pharmacokinetic Parameters of Inorganic Fluoride Following Sevoflurane Anesthesia

We studied the correlation between renal function and pharmacokinetic parameters of inorganic fluoride following sevoflurane anesthesia. In 30 neurosurgical patients aged 40–70 years, anesthesia was induced with midazolam and sevoflurane and maintained with sevoflurane and nitrous oxide in oxygen. Serum and urine inorganic fluoride (F−) levels and β2-microglobulin (BMG), blood urea nitrogen (BUN), and serum creatinine (Cr) were measured during and after anesthesia. The decrease rate of serum F− level and the area under the curve (AUC) of serum F− were calculated. Correlations among sevoflurane dosage, duration of administration, peak serum F− level, AUC, the decrease rate of serum F− level, and the maximum values in BUN, Cr, and urine BMG during the study were investigated. Urine BMG increased significantly after surgery but returned to the preoperative level in a week. BUN, Cr, and serum BMG remained within normal ranges during the study. Sevoflurane dosage and duration of administration were significantly correlated with AUC and the maximum value of urine BMG, but not with the peak serum F− level or the decrease rate of serum F−. AUC was significantly correlated with the maximum value of urine BMG. In sevoflurane anesthesia, sevoflurane dosage, duration of administration, and AUC affected urine BMG level, but not peak serum F−.

Correlation between renal function and pharmacokinetic parameters of inorganic fluoride following sevoflurane anesthesia.

We studied the correlation between renal function and pharmacokinetic parameters of inorganic fluoride following sevoflurane anesthesia. In 30 neurosurgical patients aged 40-70 years, anesthesia was induced with midazolam and sevoflurane and maintained with sevoflurane and nitrous oxide in oxygen. Serum and urine inorganic fluoride (F-) levels and β2-microglobulin (BMG), blood urea nitrogen (BUN), and serum creatinine (Cr) were measured during and after anesthesia. The decrease rate of serum F- level and the area under the curve (AUC) of serum F- were calculated. Correlations among sevoflurane dosage, duration of administration, peak serum F- level, AUC, the decrease rate of serum F- level, and the maximum values in BUN, Cr, and urine BMG during the study were investigated. Urine BMG increased significantly after surgery but returned to the preoperative level in a week. BUN, Cr, and serum BMG remained within normal ranges during the study. Sevoflurane dosage and duration of administration were significantly correlated with AUC and the maximum value of urine BMG, but not with the peak serum F- level or the decrease rate of serum F-. AUC was significantly correlated with the maximum value of urine BMG. In sevoflurane anesthesia, sevoflurane dosage, duration of administration, and AUC affected urine BMG level, but not peak serum F-.

Serum and urine inorganic fluoride levels following prolonged low-dose sevoflurane anesthesia combined with epidural block

To determine whether serum and urine inorganic fluoride levels with prolonged (more than 7 hours) low-dose (0.8 to 2.0 vol %) sevoflurane anesthesia plus epidural anesthesia were increased as compared with isoflurane anesthesia plus epidural anesthesia. To measure the urine tubular enzymes N-acetyl-beta-glucosaminidase (NAG), alpha 1-microglobulin (alpha 1-M), and beta 2-microglobulin (beta 2-M) for renal tubular injury in both groups. Randomized, prospective study. University hospital. 15 ASA physical status I and II adults (7 males, 8 females) who were scheduled for prolonged laparotomy (lasting 9.5 to 10.2 hours) with general anesthesia. Epidural anesthesia was administered before induction of general anesthesia. General anesthesia was induced with thiamylal administered intravenously (IV), and the trachea was intubated following administration of vecuronium IV. It was maintained with either sevoflurane or isoflurane in nitrous oxide and oxygen. Standard monitoring was used in all patients. Serum and urine inorganic fluoride and urine tubular enzymes were measured periodically. Serum inorganic fluoride was 54 mumol/L at 4.3 minimum alveolar concentration (MAC) hours of sevoflurane; the peak level for isoflurane was 8 mumol/L at the same MAC hours. Sevoflurane also increased urine inorganic fluoride excretion to 96 mumol/hr 8 hours. NAG excretion started to increase after inhalation of either sevoflurane or isoflurane. alpha 1-M and beta 2-M excretion increased markedly postoperatively. Even though fluoride levels and tubular enzymes were high, there was no evidence of postoperative renal dysfunction. There was no increase in urinary enzymes, which are indicators of tubular injury, specific to sevoflurane. There was no postoperative renal dysfunction, as indicated by unchanged serum creatinine and blood urea nitrogen levels.

Inorganic Fluoride in Prolonged Isoflurane Sedation

Summary An 18-year-old girl received isoflurane sedation for 48 h to facilitate mechanical ventilation. This resulted in a serum inorganic fluoride level of 37.3 μmol.l−1 when the isoflurane was stopped. As the serum fluoride level may continue to rise after isoflurane and as this level is approaching toxicity, the role of isoflurane sedation in the critically ill should be approached cautiously.

Serum and urinary inorganic fluoride levels after prolonged inhalation of sevoflurane in man

Serum and urinary inorganic fluoride levels after prolonged inhalation of sevoflurane in man

New drugs and new understandings of paediatric pharmacology

lnhalational anaesthetic agents The uptake and elimination of the inhaled anaesthetic agents in infants and children have been extensively studied. The high level of alveolar ventilation compared to the functional residual capacity, the larger proportion of vessel rich tissues, and a lower blood gas solubility coefficient all contribute to the rapid induction and recovery phases which occur in the infant. Inhalation anaesthetic agents are probably metabolized less in infants than in older patients; serum bromide levels are lower following halothane in infants than in adults. Serum inorganic fluoride levels are lower following enflurane anaesthesia, but this may also be due to increased bone deposition of fluoride in paediatric patients. The effects of the volatile anaesthetics on the cardiorespiratory system of infants and chidren are now more fully documented, lsoflurane causes an increase in heart rate and halothane slows the heart. At equal levels of anaesthesia, halothane and isoflurane cause a similar degree of hypotension which is dose-related. Isoflurane, however, causes less depression of myocardial contractility but more afterload reduction than halothane. Cardiac output is better maintained with isoflurane provided fluid is administered to maintain preload. 2 The addition of nitrous oxide to the inspired gas mixture results in cardiovascular effects which are similar to those produced by equianaesthetic dose levels of the volatile agents in oxygen. 3 While the volatile anaesthetics all cause similar increases in end-tidal carbon dioxide levels in spontaneously breathing children the patterns of ventilation differ. Depression of the ventilatory response to carbon dioxide is dose-dependent. Halothane causes tachypnoea, isoflurane causes little change in rate, and enflurane tends to slow ventilation. 4 Intercostal muscle activity is suppressed by haiothane, paradoxical breathing occurs at end-tidal concentrations above one per cent. 5 Intravenous anaesthetics and analgesics The dose requirements of thiopentone in infants and children of various ages show wide variation. Newborn infants require 3-4 mg.kg -I while those of 1-6 mo require 7-8 mg.kg-~. 6 In healthy children 5-6 mg. kg-i is the dose required for rapid reliable induction of anaesthesia. 7 The pharmacokinetics of thiopentone in paediatric patients have been studied and show a shorter elimination time in infants and children than in adults) The narcotic analgesics have been widely used in infants, especially for major surgical procedures, fentanyl being the most commonly used drug. The dose response of neonates to fentanyl indicate that a dose 10-12.5 I~g kg -I will prevent any response to surgical stimulation and provide anaesthesia for 60-90 min. 9 Older infants may require higher doses. I~ The pharmacokinetics of fentanyl depend upon age. Neonates show wider variation and slower clearance rates than older infants, who may demonstrate clearance rates higher than those of adults. ~ Preterm infants and neonates with increased intraabdominal pressure predictably demonstrate a prolonged elimination half-life of the drug. J2 Some infants demonstrate secondary peaks in plasma levels of the drug and these may be associated with respiratory depression in patients not on mechanical ventilation. The cardiovascular system is little affected by even large doses of fentanyl, but a useful effect in blunting the neonatal pulmonary vascular responses to stress has been noted. Chest wall compliance is significantly reduced by fentanyl in children.

Potential toxicity from prolonged anesthesia: A case report of a thirty-hour anesthetic

Selection of anesthetics for prolonged administration must include consideration of potential toxicity resulting from extended exposure. This report deals with a patient undergoing a 30-hour anesthetic that included nitrous oxide (N 2O) and isoflurane (9.7 MAC-hours). Serial serum inorganic fluoride levels obtained in the perioperative period demonstrated a peak fluoride level of 12.6 μmol occurring 27 hours after isoflurane was discontinued. Although higher than previously reported fluoride levels following isoflurane anesthesia in healthy adults (4 μmol), the current results are below those levels associated with renal abnormalities after prolonged enflurane anesthesia (34 μmol). In addition to outlining basic care guidelines for patients undergoing a prolonged anesthetic, this report discusses potential toxicity from prolonged exposure to both N 2O and isoflurane. It concludes that isoflurane can be tolerated in doses up to 10 MAC-hours without fluoride toxicity but cautions against the use of N 2O for periods longer than 24 hours.

Liver function and anesthetic metabolism in rats with chronic renal impairment.

Patients and rats with chronic renal insufficiency (CRI) anesthetized with enflurane do not have significantly greater increases in postoperative serum inorganic fluoride levels when compared with subjects with normal renal function. The authors chose to investigate whether this observation is due to decreased anesthetic metabolism, secondary to the renal disease. Thus, male Fischer 344 rats with surgically induced CRI were studied to determine the effect of severe renal impairment: first, on in vivo hepatic function as measured by a serum liver enzyme profile, and second, on in vitro hepatic metabolism as indicated by microsomal anesthetic defluorination rates and cytochrome P-450 levels. Rats were operated on in two stages, 1 week apart, and assigned to one of three groups. Group 1 rats had a capsule stripping of each kidney. Group 2 rats had a capsule stripping of one kidney and then a nephrectomy of the other. Group 3 rats had the upper and lower poles of one kidney excised and then a nephrectomy of the other. There was no change in renal function in rats from Group 1 and 2. Chronic renal insufficiency in Group 3 rats was manifested by threefold elevations in serum creatinine and urea nitrogen levels and reciprocal decreases in clearances. After 89-98 days, blood was obtained for a serum liver enzyme profile and rats were killed for determination of in vitro hepatic metabolism. There were no changes suggestive of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Nephrotoxicity of Fluorinated Anaesthetic Agents

SUMMARY The subject of fluorinated anaesthetic nephrotoxicity can be summarized in two figures. Figure 6 illustrates the time-course of anaesthetic defluorination following administration of methoxyflurane, enflurane and isoflurane. Figure 9 depicts changes in urinary osmolality in response to ADH administration in relationship to peak serum inorganic fluoride levels after anaesthesia. Figure 6 clearly demonstrates that the shapes of the serum inorganic fluoride curves are different after methoxyflurane, enflurane and isoflurane anaesthesia. Despite the fact that inorganic fluoride has a half-life of only 90 minutes, peak levels were maintained for three days after administration of methoxyflurane. In contrast, peak inorganic fluoride serum levels after administration of the other two agents were reached shortly after the end of anaesthesia and declined rapidly in the postanaesthetic period. To account for this prolonged elevation of fluoride levels, one has only to realize that methoxyflurane is approximately ten times more lipid soluble than either enflurane or isoflurane and that the great majority of methoxyflurane metabolism occurs in the postoperative period. Peak fluoride levels also are considerably higher after methoxyflurane anaesthesia than after administration of the other two agents. That is because methoxyflurane is biochemically more unstable than either enflurane or isoflurane and is metabolized more per unit time. Consequently, the area under the serum inorganic fluoride curve is much greater for methoxyflurane than it is for enflurane and isoflurane. Figure 9 demonstrates the strong correlation between changes in urinary osmolality after ADH administration and serum inorganic fluoride levels. Patients anaesthetized with halothane, in whom serum inorganic fluoride levels ranged from 1 to 3 /zM, showed a small increase in urinary osmolality. Volunteers anaesthetized with enflurane, in whom fluoride levels were 3 to 5 μM five days after anaesthesia, showed no change in maximum urinary osmolality, whereas an average decrease of approximately 250 mosmol/kg was seen the day after anaesthesia when the mean fluoride level was 33.6 /zM. Following high-dose methoxyflurane anaesthesia, fluoride levels ranged from 80 to 250 μM and the decrement in maximum urinary concentrating ability ranged from 400 to 600 mosmol/kg. It appears that the answers to the questions regarding inorganic fluoride nephrotoxicity are clear. Methoxyflurane is a dose-related nephrotoxin; its use should be reserved for clinical situations where it is specifically indicated, such as when a potent inhalational analgesic agent is required and when total dosage will be low (less than 2 MAC hours). Enflurane would appear to be safe in all patients, including those with mild to moderate renal impairment.

Isoniazid-induced enflurane defluorination in humans.

Serum inorganic fluoride (F-) levels were measured in 20 surgical patients treated with 300 mg isoniazid per day for periods of up to one year, prior to anesthesia with enflurane. Thirty-six control patients anesthetized with enflurane, but taking no drugs, also were studied. Regression lines for peak serum fluoride were plotted against enflurane exposure in MAC-hours. Nine isoniazid-treated patients had fluoride levels significantly (P less than 0.001) higher (y = 22.2x + 12.0) than either the 11 other isoniazid-treated patients (y = 5.0x + 8.2) or the 36 control patients (y = 5.4x + 6.3). Peak serum fluoride values in three patients exceeded 100 microM but in no patient did values exceed 10 microM by 48 h after anesthesia. It was concluded that isoniazid treatment resulted in enzyme induction in the nine patients with high peak fluoride levels. This pattern, i.e., induction occurring in approximately one-half the patients, probably is related to the genetically determined bimodal distribution of rapid and slow acetylation of isoniazid.

Effects of renal function on serum fluoride level in dogs during and after enflurane anesthesia.

To study the effect of renal function on the increased serum inorganic fluoride level produced by the metabolism of enflurane, three groups of beagle dogs were exposed to prolonged enflurane anesthesia, 1.25 MAC for 8 h. One group was studied both with and without renal function, one group only without renal function, and one group on two different occasions with renal function intact. Serum inorganic fluoride levels were determined every hour during the enflurane anesthesia and on termination for a further 4 h. In dogs with no renal function, the increase rate and the peak of serum inorganic fluoride level were significantly higher than in dogs with renal function. The average peak level in dogs with renal function was 21.4 mumol/l and in dogs with no renal function 38.4 mumol/l. Renal function was found to have the same capacity to increase the inorganic fluoride elimination from serum as other routes of elimination. At corresponding serum levels, the rate of decrease after terminating enflurane anesthesia was 3.5-4.0 mumol/l/h lower without renal function. Reanesthesia after 3 weeks did not significantly change the serum inorganic fluoride levels compared to the first anesthesia.

Renal function in Fischer 344 rats with chronic renal impairment after administration of enflurane and gentamicin.

To assess the potential for producing nephrotoxicity in rats with abnormal renal function, the renal effects of enflurane or halothane anesthesia, 1 MAC for two hours, were examined in six groups of six Fischer 344 rats each with surgically induced chronic renal impairment. As an additional predisposing factor, gentamicin, 5 mg/kg/day, was administered for one week before and for one week after anesthesia to three of the groups, one anesthetized with enflurane, one anesthetized with halothane, and one unanesthetized. No significant change in renal function could be attributed to either anesthetic agent. Serum inorganic fluoride levels four hours and 24 hours after enflurane anesthesia were similar in the gentamicin-treated and the non-gentamicin-treated groups. Clinically small but statistically significant increases in serum creatinine concentration and urinary flow occurred in all three gentamicin-treated groups during the period of treatment. Anesthesia with either enflurane or halothane in rats with chronic renal impairment treated with gentamicin did not result in additional renal damage.

Anesthesia for cesarean section--VII. Early effects on neonatal renal function of enflurane anesthesia for cesarean section.

Fourteen women undergoing elective cesarean section were anesthetized with enflurane for induction and maintenance of anesthesia. Blood enflurane and serum inorganic fluoride levels were studied in the mothers at delivery and in the neonates at delivery and in the early neonatal period. Also neonatal urinary excretion of inorganic fluoride was determined. Renal function of the neonates was tested with a sodium load at the age of 1 day. Enflurane showed the expected distribution between mothers and neonates. The enflurane level of the neonates declined rapidly after delivery. Serum inorganic fluoride level increased significantly in the mothers from start of anesthesia until delivery. The neonatal level was lower and did not reach the level of neonates in areas with a high natural fluoride content in drinking water. The level of inorganic fluoride in urine was higher than the corresponding serum level, indicating an inorganic fluoride concentrating effect of the neonatal kidney. The difference between urinary excretion and serum content of inorganic fluoride showed neonatal metabolism of enflurane. The urinary sodium excretion did not differ from that of infants delivered without halogenated inhalation agents given to the mothers.

Serum inorganic fluoride levels in obese patients during and after enflurane anesthesia.

Serum ionic fluoride levels in 24 markedly obese patients (127.6 +/- 6.0 kg) and seven nonobese control subjects (67.3 +/- 1.2 kg) were compared during and following enflurane anesthesia (less than 2.0 MAC hr). Peak serum fluoride levels were higher (28.0 +/- 1.9 vs 17.3 +/- 1.3 micrometers/L, p less than 0.01) and the rate at which fluoride levels increased was more rapid (slope 5.6 vs 2.5 micrometers/L/hr) in obese patients than in control patients. No clinical evidence of nephrotoxicity was found in either group. Vasopressin resistance tests were not performed, and thus it is inknown whether subclinical nephrotoxicity occurred in either study group. Possible reasons for increased enflurane metabolism in obesity are discussed. These possibilities include differences in fluoride ion kinetics, hepatic delivery and penetration of volatile anesthetics, and altered hepatic microsomal enzyme activity. Obesity rather than weight is an important determinant of anesthetic biotransformation.

Inorganic Fluoride Nephrotoxicity

The effects of prolonged enflurane and halothane administration on urine-concentrating ability were determined in volunteers by examining their responses to vasopressin before anesthesia and on days 1 and 5 after anesthesia. A significant decrease in maximum urinary osmolality of 264 +/- 34 mOsm/kg (26 per cent of the preanesthetic value) was present on day 1 after enflurane anesthesia, whereas subjects anesthetized with halothane had a significant increase in maximum urinary osmolality of 120 +/- 44 mOsm/kg. Serum inorganic fluoride level peaked at 33.6 muM and remained above 20 muM for approximately 18 hours. Thus, the threshold level for inorganic fluoride nephrotoxicity is lower than previously suspected.

Fluoride kinetics after enflurane anesthesia in healthy and anephric patients and in patients with poor renal function.

Enflurane, a fluorinated methylethyl ether, is metabolized, in part, to inorganic fluoride. Methoxyflurane has similar metabolism, and cases of fluoride ion-induced renal failure have been reported after its use. This prospective study was initiated to determine fluoride ion kinetics after enflurance anesthesia in 16 healthy patients, 18 anephric patients, and 6 patients each having a creatinine clearance of less than 5 ml/min (on dialysis). Serum and urine inorganic fluoride levels were determined. There was no clinical or statistical significance difference among the 3 groups with respect to maximum inorganic fluoride ion concentration or the time to reach it. The fluoride ion values were never above the 50 muM level that has been reported to cause subclinical renal toxicity. The fluoride ion concentration in serum fell rapidly after termination of anesthesia even in the anephric patients. This is presumed to be due to uptake of the ion by bone. Patients with low creatinine clearance also have low fluoride ion clearance. Statistical but not clinical significance was found in the comparison between pre-enflurane and the 24-hr fluoride ion values in the anephric and low creatine clearance patients, but this did not persist after one dialysis.