Effects of Sevoflurane and Isoflurane on Renal Function and on Possible Markers of Nephrotoxicity

Background: Low-flow sevoflurane anesthesia is associated with increasing circuit concentrations of compound A, which is nephrotoxic in rats, but the effect of compound A and low-flow sevoflurane anesthesia on renal function in humans is unclear. The authors compared the effects of high- and low-flow sevoflurane and isoflurane anesthesia on renal function and on several possible markers of nephrotoxicity in humans.

Methods: Forty-two patients without preexisting renal disease underwent either low-flow isoflurane (1 l/min, n = 14), low-flow sevoflurane (1 l/min, n = 14), or high-flow sevoflurane (6 l/min, n = 14) anesthesia for body-surface-area surgery scheduled to last at least 4 h. Twenty-four-hour urinary excretion of N-acetyl-[small beta, Greek]-glucosaminidase (NAG), [small beta, Greek]2-microglobulin, protein, glucose, blood urea nitrogen (BUN), and serum creatinine concentrations were measured before and after anesthesia.

Results: There were no differences in blood urea nitrogen, creatinine, and creatinine clearance among the three groups after anesthesia. Increased urinary N-acetyl-[small beta, Greek]-glucosaminidase excretions were seen in the low-flow and high-flow sevoflurane groups, but not in the low-flow isoflurane group (P < 0.01). Ten patients in the low-flow sevoflurane group had 24-h urinary excretion of protein that exceeded the normal ranges after anesthesia, but only one patient in the isoflurane and none in the high-flow sevoflurane groups had this.     

Effects of sevoflurane anesthesia on plasma inorganic fluoride concentrations during and after cardiac surgery

Purpose. Sevoflurane metabolism results in the production of inorganic fluoride, which is known to be nephrotoxic. Since marked changes in body temperature and hemodynamics in cardiac surgery affect sevoflurane metabolism, plasma inorganic fluoride concentrations may differ in this situation compared with other types of surgery. We therefore measured plasma inorganic fluoride concentrations during and after sevoflurane anesthesia in patients undergoing cardiac surgery. Methods. Sixteen patients undergoing coronary artery bypass grafting or valve replacement were premedicated with 5–10 mg midazolam and 0.5 mg scopolamine injected intramuscularly. Anesthesia was induced with 5–10 mg midazolam, 0.5–1 mg fentanyl, and 0.12–0.15 mg·kg⁻¹ vecuronium. Following tracheal intubation, anesthesia was maintained with oxygen, sevoflurane, and fentanyl. At the onset of cardiopulmonary bypass (CPB), sevoflurane was discontinued, and additional fentanyl, midazolam, and pancuronium were administered. Plasma inorganic fluoride concentrations were measured before anesthesia, immediately before and after CPB, and at 0, 2, 6, 12, 24, and 48 h after anesthesia. Results. The individual maximum plasma inorganic fluoride concentration was 19.2 ± 7.2 μmol·l⁻¹ (mean ± SD; range, 9.2–36.7). The mean plasma inorganic fluoride concentrations increased during anesthesia, but the rate of increase decreased after the initiation of CPB. Concentrations peaked at 2 h after anesthesia and decreased thereafter. The concentrations in three cases continued to increase 2 h after anesthesia. Conclusion. The plasma inorganic fluoride concentrations observed in patients undergoing cardiac surgery were below nephrotoxic levels. However, the decrease in mean fluoride concentration after anesthesia was slower than that in the previous study in general surgical patients. Received for publication on December 4, 1998; accepted on April 25, 1999     

Quantification of the degradation products of sevoflurane using four brands of CO2 absorbent in a standard anesthetic circuit

Purpose. CO₂ absorbents convert sevoflurane to fluoromethyl-2,2-difluoro-1-(trifluoromethyl) vinyl ether (compound A), whose toxicity in rats raises concern regarding the safety of sevoflurane in a low-flow system. The type of CO₂ absorbent is one of factors that affect compound A concentration in the anesthetic circuit. The aim of the present study was to investigate the concentration of compound A in an anesthetic model circuit following the use of different brands of soda lime and Baralyme. Methods. We measured the concentrations of compound A in four different brands of CO₂ absorbent using a low-flow (1 l·min⁻¹ fresh gas) model circuit in which 2% sevoflurane was circulated. Sodasorb II, Baralyme, Sofnolime and Wakolime-A were used as CO₂ absorbents. The concentration of compound A was measured hourly, and the temperature of the CO₂ absorbent was monitored. Results. The maximum concentration of compound A in the circuit was highest for Baralyme (25.5 ± 0.6 ppm) (mean ± SD), followed by Sodasorb II (18.9 ± 1.6 ppm), Wakolime-A (16.1 ± 0.7 ppm), and Sofnolime (15.8 ± 1.4 ppm). The maximum temperature was 50.8 ± 1.3°C for Baralyme, 48.8 ± 1.3°C for Wakolime-A, 47.0 ± 1.4°C for Sodasorb II, and 43.5 ± 3.9°C for Sofnolime. Conclusion. The relative concentrations of compound A in the low-flow circuit were Baralyme > Sodasorb II > Wakolime-A = Sofnolime. Received: August 27, 1999 / Accepted: January 13, 2000     

Effects of Low-flow Sevoflurane Anesthesia on Renal Function: Comparison with High-flow Sevoflurane Anesthesia and Low-flow Isoflurane Anesthesia

Background: The safety of low-flow sevoflurane anesthesia, during which CF2 = C(CF3)-O-CH2 F (compound A) is formed by sevoflurane degradation, in humans has been questioned because compound A is nephrotoxic in rats. Several reports have evaluated renal function after closed-circuit or low-flow sevoflurane anesthesia, using blood urea nitrogen (BUN) and serum creatinine as markers. However, these are not the more sensitive tests for detecting renal damage. This study assessed the effects of low-flow sevoflurane anesthesia on renal function using not only BUN and serum creatinine but also creatinine clearance and urinary excretion of kidney-specific enzymes, and it compared these values with those obtained in high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia.

Methods: Forty-eight patients with gastric cancer undergoing gastrectomy were studied. Patients were randomized to receive sevoflurane anesthesia with fresh gas flow of 1 l/min (low-flow sevoflurane group; n = 16) or 6-10 l/min (high-flow sevoflurane group; n = 16) or isoflurane anesthesia with a fresh gas flow of 1 l/min (low-flow isoflurane group; n = 16). In all groups, the carrier gas was oxygen/nitrous oxide in the ratio adjusted to ensure a fractional concentration of oxygen in inspired gas (FiO2) of more than 0.3. Fresh Baralyme was used in the low-flow sevoflurane and low-flow isoflurane groups. Glass balls were used instead in the high-flow sevoflurane group, with the fresh gas flow rate adjusted to eliminate rebreathing. The compound A concentration was measured by gas chromatography. Gas samples taken from the inspiratory limb of the circle system at 1-h intervals were analyzed. Blood samples were obtained before and on days 1, 2, and 3 after anesthesia to measure BUN and serum creatinine. Twenty-four-hour urine samples were collected before anesthesia and for each 24-h period from 0 to 72 h after anesthesia to measure creatinine, N-acetyl-beta-D-glucosaminidase, and alanine aminopeptidase.

Results: The average inspired concentration of compound A was 20 +/- 7.8 ppm (mean +/- SD), and the average duration of exposure to this concentration was 6.11 +/- 1.77 h in the low-flow sevoflurane group. Postanesthesia BUN and serum creatinine concentrations decreased, creatinine clearance increased, and urinary N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase excretion increased in all groups compared with preanesthesia values, but there were no significant differences between the low-flow sevoflurane, high-flow sevoflurane, and low-flow isoflurane groups for any renal function parameter at any time after anesthesia.     

Effects of Probenecid on Renal Function in Surgical Patients Anesthetized with Low-flow Sevoflurane

Background: Dehydrofluorination of sevoflurane by carbon dioxide absorbents in anesthesia machines produces compound A, which is nephrotoxic in rats. Several clinical studies indicate that prolonged low-flow sevoflurane anesthesia is associated with an increased urinary excretion of biochemical markers, such as protein. Probenecid, a competitive inhibitor of organic anion transport, diminishes compound A nephrotoxicity in rats. The purpose of the present study was to examine the effects of low- and high-flow sevoflurane anesthesia on urinary excretion of biochemical markers in humans and to examine the effects of probenecid on urinary excretion of these markers.

Methods: Elective surgical patients (n = 64) were assigned to four groups (n = 16 each): low-flow sevoflurane plus probenecid (LSP), low-flow sevoflurane (LS), high-flow sevoflurane plus probenecid (HSP), and high-flow sevoflurane (HS). Probenecid (2.0 g) was administered orally 2 h before the induction of anesthesia in both the LSP and HSP groups. Nothing was administered orally 2 h before the induction of anesthesia in either the LS or HS groups. All patients underwent prolonged low-flow (1 l/min) or high-flow (6 l/min) sevoflurane anesthesia. Urinary excretion of protein, albumin, [beta]2-microglobulin, glucose, and N-acetyl-[beta]-d-glucosaminidase was measured for up to 7 days postoperatively.

Results: Sevoflurane doses were similar in all four groups. There were no differences in blood urea nitrogen, creatinine, or creatinine clearance among the four groups after anesthesia. Average values for urinary excretion of protein, [beta]2-microglobulin, and N-acetyl-[beta]-d-glucosaminidase in the LS group were significantly higher than those in the other groups (LSP, HSP, HS;P < 0.05). There was no significant difference between the LS and LSP groups in average values for urinary excretion of albumin and glucose, although there were significant differences between the LS and both high-flow sevoflurane groups (HSP, HS).     

Improved oxygen delivery to the fetus during cesarean section under sevoflurane anesthesia with 100% oxygen

Purpose. To assess the potential benefits of sevoflurane with 100% oxygen in cesarean section in terms of oxygen delivery to the fetus, neonatal depression, and uterine contractility. Methods. Thirty-six patients undergoing elective cesarean section were enrolled. After thiamylal induction, 0.7% sevoflurane–60% nitrous oxide–40% oxygen anesthesia was administered in group G1 (n = 9), and 1.7% sevoflurane–100% oxygen anesthesia was administered in group G2 (n = 9). Spinal anesthesia under oxygen nasal prong was used in group SP (n = 18). Results. At delivery, the Po₂ values in the maternal artery and the umbilical vein and artery (MA, UV, UA) of group G2 (474 ± 50, 43 ± 9, 32 ± 9 mmHg, respectively) were significantly greater than those in groups G1 (228 ± 46, 31 ± 4, 23 ± 5 mmHg, respectively) and SP (147 ± 21, 30 ± 7, 18 ± 7 mmHg, respectively). The So₂ in the UA of group G2 (56 ± 17 %) was also greater than that in groups G1 (34 ± 10 %) and SP (32 ± 10 %). The sevoflurane concentrations at delivery in the MA, UV, and UA in group G2 were almost threefold higher than those in group G1, whereas all the newborns in the three groups had Apgar scores of 8 or more at 5 min, and the intraoperative blood loss did not differ among the groups. Conclusion. Sevoflurane anesthesia with 100% oxygen in elective cesarean delivery improves oxygen delivery to the fetus without severe neonatal depression, prolonged uterine relaxation, or increased blood loss. Received for publication on July 21, 1998; accepted on January 12, 1999     

The effects of low-flow sevoflurane and isoflurane anesthesia on renal function in patients with stable moderate renal insufficiency

Sevoflurane degrades to Compound A, which is nephrotoxic in rats. Therefore, the renal effects of Compound A is an area of intense debate. We investigated the effects of low-flow sevoflurane and isoflurane anesthesia on renal function in patients with stable renal insufficiency. Seventeen patients with a serum creatinine level of more than 1.5 mg/dL were anesthetized with sevoflurane or isoflurane at a total flow of 1 L/min. Serum creatinine and blood urea nitrogen were measured before anesthesia and again 1, 2, 3, 5, 7, and 14 days after anesthesia. The 24-h creatinine clearance was measured before anesthesia and 7 days after anesthesia. There were no significant differences in the blood urea nitrogen levels, serum creatinine concentrations, or creatinine clearance before and after anesthesia within each group. These results suggest that sevoflurane and isoflurane have similar effects on renal function in patients with moderately impaired renal function. Further study of the effects of low-flow sevoflurane anesthesia on impaired renal function with a larger sample size than ours is required to resolve the issue of sevoflurane safety in patients with renal insufficiency. IMPLICATIONS: The serum creatinine and blood urea nitrogen data indicate that, for exposures of <130 ppm/h in Compound A inspired area under the curve, renal effects of low-flow sevoflurane are similar to those of isoflurane in patients with stable renal insufficiency.     

A comparison between sevoflurane and propofol when combined with continuous epidural blockade in adult patients

Purpose. The effects of sevoflurane and propofol, in combination with continuous epidural blockade, on blood pressure control and time of recovery from anesthesia were compared. Methods. Adult patients were allocated to either a sevoflurane (n=54) or a propofol (n=64) group. Anesthesia was induced with either inhalation of 5% sevoflurane or intravenous administration of 2 mg·kg⁻¹ propofol. After an injection of vecuronium, the trachea was intubated and anesthesia was maintained with continuous epidural blockade, air/oxygen, and sevoflurane or propofol. The systolic arterial pressure was maintained within ±30% of that obtained on the ward. Results. The number of cases requiring a change in the dose of either anesthetics or vasoactive agents was not different between the groups. However, the arterial pressure and heart rate were more stable in the propofol group than in the sevoflurane group (P<0.05). The length of time before tracheal extubation was shorter in the sevoflurane group (10.4±5.2 min, mean±SD) than the propofol group (15.0±11.2 min,P<0.05). Conclusion. Propofol anesthesia, in combination with continuous epidural blockade, results in more stable intraoperative hemodynamics than sevoflurane anesthesia, but requries a longer recovery time and results in larger interindividual variability than sevoflurane anesthesia.     

Effects of sevoflurane anesthesia combined with epidural block on renal function in the elderly: comparison with isoflurane

Purpose. Renal function declines with age, but little is known about the renal effects of the inhaled anesthetic sevoflurane in the elderly. We therefore compared the renal effects of sevoflurane and isoflurane anesthesia in elderly patients. Methods. Thirteen patients aged ≥70 years undergoing gastrectomy with epidural anesthesia combined with general anesthesia were randomly assigned to receive either sevoflurane (n = 7) or isoflurane (n = 6). Dopamine (3–5 μg·kg⁻¹·min⁻¹) was administered to all patients. Blood and urine samples were collected before, during, and after anesthesia. Serum and urinary inorganic fluoride was measured, and renal function tests were performed. Results. Serum inorganic fluoride was significantly elevated in both groups. The production of inorganic fluoride was significantly greater in the sevoflurane group, but the level did not exceed 50 μmol·l⁻¹ in any patient. No abnormalities were observed in blood urea nitrogen (BUN), serum creatinine, or urine volume in either group. The albumin excretion index increased during anesthesia and decreased after anesthesia in both groups. Creatinine clearance was unchanged in the sevoflurane group but fluctuated during and after anesthesia in the isoflurane group. α₁-Microglobulin (MG), β₂-MG, and urinary N-acetyl-β-d-glucosaminidase (NAG) excretion increased up to 3 h after anesthesia, and α₁-MG and β₂-MG excretion increased on postanesthesia day 3. Conclusion. In both groups, glomerular and tubular function were transiently affected, but no abnormalities were found in routine laboratory tests, suggesting that neither isoflurane nor sevoflurane in combination with dopamine and epidural anesthesia seriously affects renal function in the elderly. Received for publication on October 23, 1998; accepted on October 27, 1999     

Compound A concentration and the temperature of CO2 absorbents during low-flow sevoflurane anesthesia in surgical patients

Sevoflurane, a new inhalational anesthetic, is metabolically broken down into several decomposition products in the presence of CO₂ absorbents. One of the products, CF₂=C (CF₃) OCH₂F (compound A), which appears to be the most toxic, was quantitated in 20 surgical patients subjected to more than 3 h of anesthesia using a low-flow anesthesia circuit. To minimize the variables in the reaction velocity between sevoflurane and the CO₂ absorbents, we maintained the sevoflurane concentration at 2%. Wakolime-A, one type of soda lime, resulted in the highest increase in compound A concentration. The peak concentration was 27.1±3.1 ppm, less than one-tenth of the LC₅₀ (50% lethal concentration) of compound A, which was previously reported as 420 or 400 ppm in rats. We also measured the temperature in CO₂ absorbents, which had been reported to influence compound A production. The elevation in the temperature was 27.9±1.3°C in Wakolime-A, 29.4±8.4°C in Baralyme, and 31.0±5.0°C in Sodasorb II. Further studies are needed to assess the safety and efficacy of sevoflurane.     

Effects of probenecid on renal function in surgical patients anesthetized with low-flow sevoflurane

BACKGROUND: Dehydrofluorination of sevoflurane by carbon dioxide absorbents in anesthesia machines produces compound A, which is nephrotoxic in rats. Several clinical studies indicate that prolonged low-flow sevoflurane anesthesia is associated with an increased urinary excretion of biochemical markers, such as protein. Probenecid, a competitive inhibitor of organic anion transport, diminishes compound A nephrotoxicity in rats. The purpose of the present study was to examine the effects of low- and high-flow sevoflurane anesthesia on urinary excretion of biochemical markers in humans and to examine the effects of probenecid on urinary excretion of these markers. METHODS: Elective surgical patients (n = 64) were assigned to four groups (n = 16 each): low-flow sevoflurane plus probenecid (LSP), low-flow sevoflurane (LS), high-flow sevoflurane plus probenecid (HSP), and high-flow sevoflurane (HS). Probenecid (2.0 g) was administered orally 2 h before the induction of anesthesia in both the LSP and HSP groups. Nothing was administered orally 2 h before the induction of anesthesia in either the LS or HS groups. All patients underwent prolonged low-flow (1 l/min) or high-flow (6 l/min) sevoflurane anesthesia. Urinary excretion of protein, albumin, beta(2)-microglobulin, glucose, and N-acetyl-beta-d-glucosaminidase was measured for up to 7 days postoperatively. RESULTS: Sevoflurane doses were similar in all four groups. There were no differences in blood urea nitrogen, creatinine, or creatinine clearance among the four groups after anesthesia. Average values for urinary excretion of protein, beta(2)-microglobulin, and N-acetyl-beta-d-glucosaminidase in the LS group were significantly higher than those in the other groups (LSP, HSP, HS; P < 0.05). There was no significant difference between the LS and LSP groups in average values for urinary excretion of albumin and glucose, although there were significant differences between the LS and both high-flow sevoflurane groups (HSP, HS). CONCLUSIONS: Low-flow sevoflurane, which produces a sevenfold higher compound A exposure than high-flow sevoflurane, resulted in significant increases of several biochemical markers in half of the patients. Probenecid appears to provide protection against these renal effects.     

Anesthesia with sevoflurane, but not isoflurane, prolongs bleeding time in humans

Purpose. Halothane has been shown to suppress platelet aggregation in vitro and ex vivo and to prolong bleeding time. In a previous in vitro study, we demonstrated that sevoflurane had a stronger suppressive effect on platelet aggregation than halothane. The present study investigated whether clinical use of sevoflurane affects bleeding time in vivo. Methods. Thirty-four patients undergoing minor elective surgery were randomly assigned to sevoflurane or isoflurane. Anesthesia was induced with intravenous thiopental and maintained with sevoflurane or isoflurane with nitrous oxide. Bleeding time was measured by the Duke method. An initial (control) measurement was obtained in the operating room before the induction of anesthesia, and a second was obtained 5–10 min after endotracheal intubation but before starting the operation, when the end-expiratory concentration of sevoflurane or isoflurane had been stabilized at 1–1.5 times the minimum alveolar concentration (MAC), and the mean arterial pressures were between 80% and 120% of the preanesthetic values. Results. Bleeding time was increased from the preanesthetic value of 2.07 ± 0.82 min to 2.83 ± 0.93 min (n = 15) in the sevoflurane group (P < 0.01) but was not significantly altered in the isoflurane group. Conclusion. Sevoflurane alters bleeding time in the clinical situation. Received for publication on May 28, 1998; accepted on June 8, 1999     

Compound A: Toxikologie und klinische Relevanz

Sevoflurane, like all currently used volatile anaesthetics, is degraded by carbon dioxide absorbents. The most significant degradant is a haloalkene known trivially as ”compound A”. Compound A is nephrotoxic in rats and, at higher doses, in nonhuman primates, causing proximal tubular necrosis. There has been much interest in the potential for compound A toxicity in humans. Inhaled compound A concentrations are greatest at low flow rates, high sevoflurane concentrations, warmer absorbent, barium hydroxide vs soda lime, and drier absorbent. Typical inspired compound A concentrations during low-flow and closed-circuit sevoflurane anaesthesia in humans are 8–24 and 20–32 ppm with soda lime and barium hydroxide lime, respectively. Renal effects of compound A production during sevoflurane anesthesia have been examined in surgical patients and volunteers, using standard (creatinine clearance, serum BUN and creatinine) and experimental (urine excretion of protein, glucose, NAG, GST, AAP) markers of renal function. Investigations to date in surgical patients show similar renal effects of low-flow sevoflurane, low-flow isoflurane or high-flow sevoflurane. There have been no case reports of compound A-associated renal injury in humans. In volunteers, one study found changes in experimental but not conventional renal markers, while other investigations show no significant changes in either standard or experimental markers. The mechanism of compound A nephrotoxicity in rats appears to involve metabolism to glutathione and cysteine conjugates, and their subsequent renal uptake and metabolism by pathways that are different in rats and humans.     

Epidural anesthesia during hysterectomy diminishes postoperative pain and urinary cortisol release

Purpose To examine the hypothesis that epidural anesthesia throughout lower abdominal surgery would depress both postoperative pain and cortisol release. Methods Forty adult patients undergoing abdominal total hysterectomy were studied. The patients were randomly assigned to two groups. Group G received general anesthesia alone (sevoflurane 1.5%–2.5%); group E received a combination of epidural anesthesia (1.5% mepivacaine) with a light plane of general anesthesia (sevoflurane<0.5%). Postoperative analgesia was obtained epidurally by patient-controlled analgesia. Postoperative pain at rest and during movement was assessed by a visual analogue scale (VAS) at 2, 24, and 48 h following surgery. The plasma concentration and urinary excretion of cortisol were measured during the perioperative period. Results VAS values were lower in group E than in group G during movement at 24h (4.6±0.5vs 6.1±0.4 cm). Urinary cortisol excretion on the first postoperative day was less in group E than in group G (192±34vs 480±120μg). Conclusions Epidural blockade prior to surgical stimuli and throughout lower abdominal surgery reduces the postoperative dynamic pain and stress response.     

Effects of sevoflurane and isoflurane on the ratio of cerebral blood flow/metabolic rate for oxygen in neurosurgery

Purpose. To examine the changes in cerebral blood flow (CBF) equivalent (CBF divided by cerebral metabolic rate for oxygen) during craniotomy under isoflurane and sevoflurane anesthesia in patients with intracranial disorders. Method. In 16 neurosurgical patients (8 anesthetized with isoflurane and 8 with sevoflurane), the CBF equivalent was measured while the end-tidal concentration of the selected volatile anesthetic was maintained at 0.5 and 1.0 minimum alveolar concentration (MAC) before surgery, and then 1.0 MAC during surgery, which lasted more than 4 h. Results. There was no significant difference in CBF equivalent at 0.5 MAC between the isoflurane (20 ± 4 ml blood/ml oxygen) and the sevoflurane (19 ± 4 ml blood/ml oxygen) groups. With increasing anesthetic depth from 0.5 to 1.0 MAC, the CBF equivalent significantly (P < 0.05) increased in both groups (22 ± 7 and 21 ± 5, respectively). At 1.0 MAC during operation, the CBF equivalent with both anesthetics was maintained with minimal fluctuation for 4 h. There were no significant differences in the average value of the CBF equivalent during a 4-h period at 1.0 MAC between the isoflurane (23 ± 5) and the sevoflurane (20 ± 4) groups. Conclusion. Deepening anesthesia from 0.5 to 1.0 MAC with isoflurane and sevoflurane produced a slight increase in the CBF equivalent. The CBF equivalent at 1.0 MAC was maintained with no difference between the two agents during 4 h of neurosurgery. Received: August 2, 1999 / Accepted: April 3, 2000     

Urinary biomarkers in assessing the nephrotoxic potential of gentamicin in solitary kidney patients after 7 days of therapy

Introduction: The solitary kidney (SK) may present increased vulnerability to nephrotoxicity because of adaptive phenomena. Aims: Assessing the vulnerability of the SK with urinary tract infections (UTI) to gentamicin by means of urinary biomarkers (N-acetyl-beta-D-glucosaminidase (NAG) and urinary alpha-1-microglobulin), as well as glomerular filtration rate (GFR). Methods: We studied 14 patients with SK with UTI (group A) (mean age 58.07?±?13.61 years, mean duration of SK 13.55?±?12.33 years) who were administered gentamicin for 7 days. Group B consisted by 17 patients with SK without any other associated renal pathology (average age 51.17?±?9.39 years, average existence period of a single kidney 33.23?±?21.73 years). We also included a third group (group C) represented by nine healthy individuals, with two kidneys. Results: Increased values of urinary NAG were found in group B as compared to group C and alpha-1 microglobulin in group A as compared to group B. During treatment with gentamicin, increased values of both NAG and alpha-1-microglobulin in group A were found on day 7 as compared to values before treatment (day 7 NAG?=?18.99?±?14.07?U/g creat versus day 0, NAG?=?5.15?±?6.54?U/g creat, p?=?0.004; day 7 alpha-1-microglobulin?=?20.88?±?18.84?mg/g creat versus day 0, urinary alpha-1-microglobulin?=?4.96?±?6.57?mg/g creat, p?=?0.003). No statistically significant alterations of GFR were noticed after 7 days of treatment. Conclusions: We found the nephrotoxic effects of gentamicin at tubular level, but not at glomerular level. The nephrotoxic potential of gentamicin in patients with a SK can be monitored by assessing urinary biomarkers during treatment of UTI.     

Effects of age on neuromuscular blockade by vecuronium as measured by accelography under sevoflurane anesthesia

We evaluated possible differential effects of age on a single bolus intravenous injection of vecuronium using accelography under sevoflurane anesthesia. Thirty anesthetized patients were divided into three groups of 10 patients as follows: group 1=age 1–5 years; group 2=age 20–40 years, and group 3=age >70 years. Vecuronium 0.1 mg·kg⁻¹ was given to facilitate tracheal intubation. Onset time, i.e., the time from the start of injection of the first dose of vecuronium to development of maximal twitch depression in group 1 was significantly shorter than those in groups 2 and 3 (103.5±30.4s, 166.5±32.7s, and 202.5±56.7s; mean±SD;P<0.01). Clinical duration, i.e., the time from completion of maximal block to 25% recovery of train-of-four (TOF) ratio in group 1 was significantly shorter than that in group 3 (43.6±12.0 min and 67.3±15.6 min;P<0.01). The reversal time from 25% to 75% of the TOF ratio after the administration of neostigmine in group 1 was not significantly different from those in groups 2 and 3 (172.5±73.9s, 219.0±59.7s, and 222.0±155.7s). The authors conclude that the time to maximal twitch depression after the administration of vecuronium is significantly shorter in children than that in adults, and that the fastest recovery from vecuronium is also observed in children.     

Long-duration low-flow sevoflurane and isoflurane effects on postoperative renal and hepatic function.

Sevoflurane degradation by carbon dioxide absorbents during low-flow anesthesia forms the haloalkene Compound A, which causes nephrotoxicity in rats. Numerous studies have shown no effects of Compound A formation on postoperative renal function after moderate-duration (3-4 h) low-flow sevoflurane; however, effects of longer exposures remain unresolved. We compared renal function after long-duration low-flow (<1 L/min) sevoflurane and isoflurane anesthesia in consenting surgical patients with normal renal function. To maximize degradant exposure, Baralyme was used, and anesthetic concentrations were maximized (no nitrous oxide and minimal opioids). Inspired and expired Compound A concentrations were quantified. Blood and urine were obtained for laboratory evaluation. Sevoflurane (n = 28) and isoflurane (n = 27) groups were similar with respect to age, sex, weight, ASA status, and anesthetic duration (9.1 +/- 3.0 and 8.2 +/- 3.0 h, mean +/- SD) and exposure (9.2 +/- 3.6 and 9.1 +/- 3.7 minimum alveolar anesthetic concentration hours). Maximum inspired Compound A was 25 +/- 9 ppm (range, 6-49 ppm), and exposure (area under the concentration-time curve) was 165 +/- 95 (35-428) ppm. h. There was no significant difference between anesthetic groups in 24- or 72-h serum creatinine, blood urea nitrogen, creatinine clearance, or 0- to 24-h or 48- to 72-h urinary protein or glucose excretion. Proteinuria and glucosuria were common in both groups. There was no correlation between Compound A exposure and any renal function measure. There was no difference between anesthetic groups in 24- or 72-h aspartate aminotransferase or alanine aminotransferase. These results show that the renal and hepatic effects of long-duration low-flow sevoflurane and isoflurane were similar. No evidence for low-flow sevoflurane nephrotoxicity was observed, even at high Compound A exposures as long as 17 h. Proteinuria and glucosuria were common and nonspecific postoperative findings. Long-duration low-flow sevoflurane seems as safe as long-duration low-flow isoflurane anesthesia. IMPLICATIONS: Postoperative renal function after long-duration low-flow sevoflurane (with Compound A exposures greater than those typically reported) and isoflurane anesthesia were not different, as assessed by serum creatinine, blood urea nitrogen, and urinary excretion of protein and glucose. This suggests that low-flow sevoflurane is as safe as low-flow isoflurane, even at long exposures.     

Comparison between sevoflurane and isoflurane anesthesia in pig hepatic ischemia-reperfusion injury

Purpose. Sevoflurane and isoflurane have been reported to exert protective effects against ischemia-reperfusion injury (IRI) in various organs. To compare the effect of sevoflurane anesthesia on liver IRI with that of isoflurane anesthesia, we performed the present study in pigs. Methods. Nineteen pigs were assigned to either the sevoflurane (n = 9) or the isoflurane group (n = 10). Hepatic warm ischemia was produced by 30-min hepatic artery and portal vein clamping beginning 90 min after the start of the inhalation anesthesia; this was followed by a 240-min reperfusion. To extend our evaluation, we evaluated the degree of IRI using various parameters (plasma α-glutathione-S-transferase [α-GST], lipid peroxide, and lactate concentrations), in addition to the conventionally used liver damage markers. Results. The lactate level was significantly higher under isoflurane than under sevoflurane at 120 min after reperfusion (4.0 ± 0.4 mmol·l⁻¹ vs 2.5 ± 0.3 mmol·l⁻¹; P < 0.05). How-ever, this difference had disappeared after 240 min of reperfusion. No significant differences between the two groups were observed in values for α-GST, lipid peroxides, aspartate aminotransferase, alanine aminotransferase, or lactic dehydrogenase. Conclusion. The extent of the hepatic IRI seen under sevoflurane anesthesia in pigs did not differ significantly from that seen under isoflurane, as judged from measurements of a number of parameters over a 240-min reperfusion period. Received: February 14, 2001 / Accepted: August 28, 2001     

Effects of nicardipine-induced hypotension on cerebrovascular carbon dioxide reactivity in patients with diabetes mellitus under sevoflurane anesthesia

Purpose The purpose of this study was to examine the effects of nicardipine-induced hypotension on cerebrovascular CO₂ reactivity in patients with diabetes mellitus under sevoflurane anesthesia. Methods Nineteen diabetic patients, and 11 nondiabetic patients (serving as controls), undergoing elective orthopedic, cardiovascular, or thoracic surgery were included in the study. The diabetic patients were divided into three groups according to the antidiabetic therapy they were receiving, i.e., diet therapy (n = 6), oral antidiabetic drugs (n = 7), and insulin (n = 6). Anesthesia was maintained with 1.0 minimum alveolar concentration of sevoflurane. Absolute and relative cerebrovascular CO₂ reactivity was calculated using a 2.5-MHz pulsed transcranial Doppler (TCD) probe for the continuous measurement of mean blood flow velocity in the middle cerebral artery (Vmca). The cerebrovascular CO₂ reactivity was measured both at baseline and during hypotension by increasing the ventilatory frequency by 4 to 7 breaths·min⁻¹. Nicardipine was used to induce hypotension. Results We found that values for the Bispectral index (BSI), baseline mean blood pressure, endtidal CO₂ (Pet_{CO 2}), and Vmca were essentially identical in all patients, irrespective of the type of antidiabetic treatment being taken. Values for absolute and relative CO₂ reactivity in insulin-dependent patients, at both baseline blood pressure and during hypotension, were lower than those in patients in the antidiabetic drug, diet, and control groups (during hypotension, absolute CO₂ reactivity: diet group: 3.2 ± 0.9; oral antidiabetic drug group: 3.2 ± 0.7; insulin group: 1.5 ± 0.6; control group: 3.4 ± 0.8 cm·s⁻¹·mmHg⁻¹, [P < 0.05 insulin group vs the other groups]; relative CO₂ reactivity: diet group, 6.3 ± 1.0; oral antidiabetic drug group, 6.5 ± 0.8; insulin group, 3.5 ± 0.8; control group, 6.5 ± 0.7%·mmHg⁻¹, [P < 0.05 insulin group vs the other groups]. Conclusion We concluded that cerebrovascular CO₂ reactivity in insulin-dependent patients is impaired during nicardipine-induced hypotension under sevoflurane anesthesia.