Oral clonidine premedication reduces minimum alveolar concentration of sevoflurane for tracheal intubation in children

BACKGROUND: Sevoflurane is a useful anesthetic for inhalational induction in children because of its low solubility in blood and relatively nonpungent odor. Clonidine has sedative and anxiolytic properties and reduces the requirement for inhalation agents. Nitrous oxide (N2O) also decreases the requirement of inhaled anesthetics, but the effect is variable. The minimum alveolar concentration for tracheal intubation (MAC(TI)) of sevoflurane was assessed with and without N2O and clonidine premedication. METHODS: Seventy-two patients, aged 3-11 yr, were assigned to one of six groups (n = 12 each). They received one of three preanesthetic medications (two groups for each premedication): placebo (control), 2 microg/kg oral clonidine or 4 microg/kg oral clonidine. In one group of each premedication, anesthesia was induced with sevoflurane in oxygen; in the other group, anesthesia was induced with sevoflurane in the presence of 60% N2O. Each concentration of sevoflurane at which tracheal intubation was attempted was predetermined according to Dixon's up-and-down method and held constant for at least 20 min before the trial RESULTS: The MAC(TI) of sevoflurane in the absence of N2O (mean +/- SEM) was 3.2 +/- 0.2%, 2.5 +/- 0.1%, and 1.9 +/- 0.2% in the control, 2-microg/kg clonidine, and 4-microg/kg clonidine groups, respectively. Nitrous oxide (60%) decreased the MAC(TI) of sevoflurane by 26%, 24%, and 27% in the control, 2-microg/kg clonidine, and 4-microg/kg clonidine groups. CONCLUSIONS: Oral clonidine premedication decreased the MAC(TI) of sevoflurane. Nitrous oxide also decreased the MAC(TI). The combination of clonidine and N2O lessened the MAC(TI) of sevoflurane more than did either drug alone.     

Repeated low-flow sevoflurane anesthesia: effects on hepatic and renal function in beagles

We studied the effects of repeated low-flow sevoflurane anesthesia for 6 hours. Five beagle dogs received 1.3 MAC (3%) sevoflurane anesthesia. Anesthesia of 6 hours was repeated on at the 7th day after the first anesthesia. Compound A gas samples were collected from the inspiratory limb during anesthesia. Concentrations of serum and renal fluoride, hepatic and renal function parameters were measured during and up to 7 days after the first and second anesthesia. The peak concentration of compound A was 23.7 +/- 3.6 ppm at 2 hours and the same level remained during the anesthesia. Plasma fluoride level exceeded 50 mmol.l-1 during anesthesia and rapidly decreased to the preanesthesia level thereafter. Serum GOT increased slightly only on the first postanesthesia day. No significant changes in other blood chemistry studies were observed. The excretion of renal tubular enzymes did not increase during and after anesthesia. Repeated low flow sevoflurane anesthesia in beagles did not affect hepatic and renal function significantly.     

Hypoxemia decreases the shivering threshold in rabbits anesthetized with 0.2 minimum alveolar anesthetic concentration isoflurane

Shivering has been proposed as an etiology of postoperative hypoxemia. The difficulty with this theory is that hypoxemia inhibits shivering in unanesthetized cats, rats, and humans. However, anesthesia inhibits many protective reflexes, including the ventilatory response to hypoxemia. We therefore tested the hypothesis that arterial hypoxemia fails to inhibit shivering in lightly anesthetized rabbits. Rabbits were intubated and instrumented during exposure to surgical concentrations of anesthesia, and anesthesia was then maintained with 0.2 minimum alveolar anesthetic concentration isoflurane. The core was cooled at a rate of 2-3 degrees C/h by perfusing water at 10 degrees C through a colonic thermode. Core temperatures were recorded from the distal esophagus. Sustained, vigorous shivering was considered physiologically significant. The core temperature that triggering significant shivering identified the thermoregulatory threshold for this response. Arterial blood was sampled for gas analysis at the shivering threshold in each rabbit. Hypoxemia linearly reduced the shivering threshold from 36.7 degrees C at 130 mm Hg to 35.4 degrees C at 50 mm Hg (threshold = PaO2.0.019 + 34.3; r2 = 0.49). We failed to confirm our hypothesis: instead, even mild hypoxemia reduced the shivering threshold >1 C. A 1 C decrease in the shivering threshold is likely to prevent or stop most postoperative shivering because it exceeds the reduction produced by many effective anti-shivering drugs. These data do not support the theory that shivering causes postoperative hypoxemia. IMPLICATIONS: Shivering has been proposed as an etiology of postoperative hypoxemia. Our data, in contrast, show that mild hypoxemia inhibits shivering. Shivering is thus unlikely to be a cause of postoperative hypoxemia.     

Minimum alveolar anesthetic concentrations for airway occlusion in cats: a new concept of minimum alveolar anesthetic concentration-airway occlusion response

The role of ergosterol in yeast stress tolerance, together with heat shock proteins (hsps) and trehalose, was examined in a sterol auxotrophic mutant of Saccharomyces cerevisiae. Ergosterol levels paralleled viability data, with cells containing higher levels of the sterol exhibiting greater tolerances to heat and ethanol. Although the mutant synthesised hsps and accumulated trehalose upon heat shock to the same levels as the wild-type cells, these parameters did not relate to stress tolerance. These results indicate that the role of ergosterol in stress tolerance is independent of hsps or trehalose.     

Ethanol concentrations approaching minimum alveolar anesthetic concentration are required to suppress learning in a fear-potentiated startle paradigm in rats

We previously demonstrated that desflurane and two nonimmobilizers dose-dependently decrease learning and memory in rats. This suggests that although they do not suppress movement in response to noxious stimuli, nonimmobilizers act like inhaled anesthetics in their effects on learning and memory. Like most conventional anesthetics, nonimmobilizers have a greater affinity for lipid than for aqueous phases. In the present study, we examined the effect of ethanol on learning and memory to test the hypothesis that a large part of the capacity of anesthetics to affect learning depends on an action on a lipid (nonpolar) phase. Unlike volatile anesthetics and nonimmobilizers, ethanol has a greater affinity for water than for lipids. Thus, if our hypothesis is correct, ethanol should be relatively less potent in its suppression of memory. Rats receiving various doses of ethanol were conditioned to fear a light followed by a footshock. Fear conditioning to the light was subsequently assessed by measurement of potentiation of the acoustic startle reflex in the presence, compared with the absence, of light. Ethanol up to 0.54 minimum alveolar anesthetic concentration (MAC) did not abolish fear, but 0.82 MAC ethanol did abolish learning. Expressed as a fraction of MAC or predicted MAC, ethanol is less potent than desflurane or the nonimmobilizer 1,2-dichlorohexafluorocyclobutane in suppressing learning. This finding is consistent with the hypothesis that the capacity of anesthetics and nonimmobilizers to impair learning and memory depends mostly on an action at a nonpolar site. IMPLICATIONS: Abolition of learning and memory is an important property of inhaled anesthetics. This effect primarily results from an action at a lipid (nonpolar) site, rather than a polar site or a water-lipid interface.     

Effect of intravenous lidocaine on halothane minimum alveolar concentration in ponies

This study investigated the effect of lidocaine i.v. on halothane minimum alveolar concentration (MAC) in ponies. Six ponies were anaesthetised with thiopentone and succinylcholine, intubated and anaesthesia maintained with halothane. Ventilation was controlled and blood pressure maintained within clinically acceptable limits. Following a 2 h equilibration period, baseline halothane MAC was determined. The ponies were then given a loading dose of lidocaine (2.5 or 5 mg/kg bwt) or saline over 5 min, followed by a constant infusion of lidocaine (50 or 100 microg/kg/min, or saline, respectively). The halothane MAC was redetermined after a 60 min infusion of lidocaine or saline. The baseline halothane MAC for the control group was mean +/- s.d. 0.94 +/- 0.03%, and no significant decrease occurred following saline infusion. Lidocaine decreased halothane MAC in a dose-dependent fashion (r = 0.86; P < 0.0003). The results indicate that i.v. lidocaine may have a role in equine anaesthesia.     

Influence of sevoflurane and isoflurane anesthesia on renal function in elderly patients

We examined the influence of sevoflurane and isoflurane anesthesia on renal function in elderly patient who underwent gastrectomy. Plasma inorganic fluoride level was significantly higher in sevoflurane group compared with isoflurane group from 3 hours after the beginning of anesthesia to the 3rd operative day. In contrast, parameters such as urinary beta 2 microglobulin, urinary N-acetyl-beta-D-glucosaminidase, and urinary gamma-GTP activities increased in both groups, but the increase was not significant. Serum BUN and creatinine levels were within normal limits. These results suggest that elderly patients without renal dysfunction appear unlikely to have any significant problem after prolonged sevoflurane anesthesia.     

Renal function in patients during and after hypotensive anesthesia with sevoflurane

STUDY OBJECTIVES: To evaluate renal function during and after hypotensive anesthesia with sevoflurane compared with isoflurane in the clinical setting. DESIGN: Randomized, prospective study. SETTING: Inpatient surgery at Rosai Hospital. PATIENTS: 26 ASA physical status I and II patients scheduled for orthopedic surgery. INTERVENTIONS: Patients received isoflurane, nitrous oxide (N2O), and fentanyl (Group I = isoflurane group; n = 13) or sevoflurane, N2O, and fentanyl (Group S = sevoflurane group; n = 13). Controlled hypotension was induced with either isoflurane or sevoflurane to maintain mean arterial pressure at 60 mmHg for 120 minutes. MEASUREMENTS AND MAIN RESULTS: Measurements included serum inorganic fluoride (previously speculated to influence renal function), creatinine clearance (CCr; to assess renal glomerular function), urinary N-acetyl-beta-D-glucosaminidase (NAG; to assess renal tubular function), blood urea nitrogen (BUN), and serum creatinine (as clinical renal function indices). Serum fluoride, CCr, and NAG were measured before hypotension, 60 minutes, and 120 minutes after the start of hypotension, 30 minutes after recovery of normotension, and on the first postoperative day. BUN and serum creatinine were measured preoperatively and on the third and seventh postoperative days. Minimum alveolar concentration times hour was 3.6 +/- 1.8 in Group I and 4.0 +/- 0.7 in Group S. In both groups, BUN and serum creatinine did not change, and CCr significantly decreased after the start of hypotension. In Group I, serum fluoride and NAG did not change. In Group S, serum fluoride significantly increased after the start of hypotension compared with prehypotension values and compared with Group I values. In addition, NAG significantly increased at 120 minutes after the start of hypotension and at 30 minutes after recovery of normotension, but returned to prehypotension values on the first postoperative day. CONCLUSIONS: Two hours of hypotensive anesthesia with sevoflurane under 5 L/min total gas flow in patients having no preoperative renal dysfunction transiently increased NAG, which is consistent with a temporary, reversible disturbance of renal tubular function.     

Changes in vitamin E concentration after surgery and anesthesia

The aim of this randomized study was to examine changes in vitamin E concentration in female subjects (age 30-60, ASA I) after cholecystectomy and halothane (N = 16) or isoflurane (N = 16) anaesthesia. Vitamin E concentration was measured two days before, and then one, five and twenty-four hours and four days after surgery. High-pressure liquid chromatography was used for its determination. Simultaneously activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) were determined. Statistical analysis: ANOVA, Tukay HSD test. The research has been accepted by the Drugs Committee of the Karlovac County Hospital. Preoperative vitamin E concentrations in the halothane group were 8.69 +/- 2.35 micrograms/L, median 8.67 micrograms/L and in the isoflurane group 9.43 +/- 2.4 micrograms/L, median 9.08 micrograms/L. Statistically lower vitamin E concentrations compared with preoperative values were noted one hour (P < 0.05), 5 hours (P < 0.01), 24 hours (P < 0.01), as well as 4 days (P < 0.01) after the operation. The lowest vitamin E concentrations were noted 24 hours after the operation with statistically insignificantly higher values in the isoflurane group (halothane group 5.98 +/- 2.08 micrograms/L, isoflurane group 6.58 +/- 1.51 micrograms/L). Analyzing enzyme (ALT, AST and GGT) pre- and postoperative values, no statistically significant differences between the investigated groups and during the time were observed. Statistically significant differences were found between individual measurement times, with no statistical significance of the differences between the halothane and isoflurane groups. It seems that neither the difference in halothane and isoflurane biotransformation nor their distinct effect on perfusion of some organs are the determining factors in post-operative changes in vitamin E concentration.     

Antiemetic activity of propofol after sevoflurane and desflurane anesthesia for outpatient laparoscopic cholecystectomy

BACKGROUND: Controversy exists regarding the effectiveness of propofol to prevent postoperative nausea and vomiting. This prospective, randomized, single-blinded study was designed to evaluate the antiemetic effectiveness of 0.5 mg/kg propofol when administered intravenously after sevoflurane- compared with desflurane-based anesthesia. METHODS: Two hundred fifty female outpatients undergoing laparoscopic cholecystectomy were assigned randomly to one of four treatment groups. All patients were induced with intravenous doses of 2 mg midazolam, 2 microg/kg fentanyl, and 2 mg/kg propofol and maintained with either 1-4% sevoflurane (groups 1 and 2) or 2-8% desflurane (groups 3 and 4) in combination with 65% nitrous oxide in oxygen. At skin closure, patients in groups 1 and 3 were administered 5 ml intravenous saline, and patients in groups 2 and 4 were administered 0.5 mg/kg propofol intravenously. Recovery times were recorded from discontinuation of anesthesia to awakening, orientation, and readiness to be released home. Postoperative nausea and vomiting and requests for antiemetic rescue medication were evaluated during the first 24 h after surgery. RESULTS: Propofol, in an intravenous dose of 0.5 mg/kg, administered at the end of a sevoflurane-nitrous oxide or desflurane-nitrous oxide anesthetic prolonged the times to awakening and orientation by 40-80% and 25-30%, respectively. In group 2 (compared with groups 1, 3, and 4), the incidences of emesis (22% compared with 47%, 53%, and 47%) and requests for antiemetic rescue medication (19% compared with 42%, 50%, and 47%) within the first 6 h after surgery were significantly lower, and the time to home-readiness was significantly shorter in duration (216 +/- 50 min vs. 249 +/- 49 min, 260 +/- 88 min, and 254 +/- 72 min, respectively). CONCLUSIONS: A subhypnotic intravenous dose of propofol (0.5 mg/kg) administered at the end of outpatient laparoscopic cholecystectomy procedures was more effective in preventing postoperative nausea and vomiting after a sevoflurane-based (compared with a desflurane-based) anesthetic.     

Induction of anesthesia and tracheal intubation with sevoflurane in adults

BACKGROUND: The speed, quality, and cost of mask induction of anesthesia and laryngeal mask airway insertion or tracheal intubation were studied in young non-premedicated volunteers given high inspired concentrations of sevoflurane (6 to 7%). METHODS: Twenty healthy persons who were 19 to 32 years old participated three times, received 6 l/min fresh gas flow, and were randomized to receive 6 to 7% sevoflurane in 66% nitrous oxide/28% oxygen by face mask until tracheal intubation (treatment 1) or until laryngeal mask airway insertion (treatment 3), or 6 to 7% sevoflurane without nitrous oxide to tracheal intubation (treatment 2). Participants exhaled to residual volume and took three vital capacity breaths of the gas mixture; thereafter ventilation was manually assisted. The time of exposure to the inhaled gas was varied for consecutive participants. It was either increased or decreased by 30-sec increments based on the failure or success of the preceding volunteer's response to laryngoscopy and intubation after a preselected exposure time. Failure was defined as poor jaw relaxation, coughing or bucking, or inadequate vocal cord relaxation. RESULTS: Loss of the lid-lash reflex in unpremedicated young volunteers was achieved in 1 min and did not differ among groups. Average time (and 95% confidence interval) for acceptable conditions for LMA insertion was achieved in 1.7 (0.7 to 2.7) min, and all participants had an immediate return of spontaneous ventilation. The time for acceptable tracheal intubating conditions after manual hyperventilation by mask was 4.7 (3.7 to 5.7) min and 6.4 (5.1 to 7.7) min in treatments 1 and 2, respectively. There were no cases of increased secretions or laryngospasm. The incidence of breath holding and expiratory stridor ("crowing") was 7.5% and 25%, respectively, during treatment 1 and 15% and 40%, respectively, during treatment 2. CONCLUSIONS: The induction of anesthesia to loss of lid reflex in young non-premedicated adults approaches the speed of intravenous induction techniques. No untoward airway responses were noted during mask induction of anesthesia with a three-breath technique. In response to intubation, no adverse airway responses, including jaw tightness, laryngospasm, and excessive coughing or bucking, occurred in participants whose duration of mask administration of sevoflurane met the appropriate times (as determined in this study).     

Changes in mandibular alveolar bone and anterior face height after four years of complete denture wearing

A 4-year cephalometric study was conducted on 14 wearers of complete dentures to quantify the anterior alveolar bone loss and to study any associated changes in the maxillomandibular relationships. Both the occlusal and the rest-face heights underwent a significant decrease while a parallel tendency for anterior rotation was recorded. The continuous bone loss in the anterior mandible had a significant relationship to the reduction of the anterior face height.     

Cyclosporine trough concentrations in predicting allograft rejection and renal toxicity up to 12 months after renal transplantation

We recently identified a novel gene (PB39) (HGMW-approved symbol POV1) whose expression is up-regulated in human prostate cancer using tissue microdissection-based differential display analysis. In the present study we report the full-length sequencing of PB39 cDNA, genomic localization of the PB39 gene, and genomic sequence of the mouse homologue. The full-length human cDNA is 2317 nucleotides in length and contains an open reading frame of 559 amino acids which does not show homology with any reported human genes. The N-terminus contains charged amino acids and a helical loop pattern suggestive of an srp leader sequence for a secreted protein. Fluorescence in situ hybridization using PB39 cDNA as probe mapped the gene to chromosome 11p11.1-p11.2. Comparison of PB39 cDNA sequence with murine sequence available in the public database identified a region of previously sequenced mouse genomic DNA showing 67% amino acid sequence homology with human PB39. Based on alignment and comparison to the human cDNA the mouse genomic sequence suggests there are at least 14 exons in the mouse gene spread over approximately 100 kb of genomic sequence. Further analysis of PB39 expression in human tissues shows the presence of a unique splice variant mRNA that appears to be primarily associated with fetal tissues and tumors. Interestingly, the unique splice variant appears in prostatic intraepithelial neoplasia, a microscopic precursor lesion of prostate cancer. The current data support the hypothesis that PB39 plays a role in the development of human prostate cancer and will be useful in the analysis of the gene product in further human and murine studies.     

Pharmacokinetics of dolasetron after oral and intravenous administration of dolasetron mesylate in healthy volunteers and patients with hepatic dysfunction

In previous studies, dolasetron was shown to have both renal and hepatic elimination mechanisms. This study was conducted to determine the impact of varying degrees of hepatic dysfunction on the pharmacokinetics and safety of dolasetron and its reduced metabolites. Seventeen adults were studied: six healthy volunteers (group I), seven patients with mild hepatic impairment (Child-Pugh class A; group II), and four patients with moderate to severe hepatic impairment (Child-Pugh class B or C1; group III). Single 150-mg doses of dolasetron mesylate were administered intravenously and orally, with a 7-day washout period separating treatments. After intravenous administration, no differences were observed between healthy volunteers and patients with hepatic impairment in maximum plasma concentration (Cmax), areas under the plasma concentration-time curve (AUC), or elimination half-life (t1/2) of intact dolasetron. No significant differences were found in Cmax, AUC, or apparent clearance (C(lapp)) of hydrodolasetron, the primary metabolite of dolasetron. The mean t1/2 increased from 6.87 hours in group I to 11.69 hours in group III. After oral administration, C(lapp) of hydrodolasetron decreased by 42%, and Cmax increased by 18% in patients with moderate to severe hepatic impairment. There were less changes in patients with mildly hepatic impairment. Total percentage of dose excreted as metabolites was similar for healthy volunteers and patients with hepatic impairment, although urinary metabolite profiles differed slightly. Dolasetron was well tolerated and there were no apparent differences in adverse effects between groups or treatments. Because hepatic impairment did not influence Cl(app) of hydrodolasetron after intravenous administration, and the range of plasma concentrations of hydrodolasetron after oral administration was not different from those observed in healthy volunteers, dosage adjustments are not recommended for patients with hepatic disease and normal renal function.     

Failure of enflurane and halothane anesthesia to inhibit lymphocyte transformation in volunteers

Changes in the peripheral blood leukocyte count and in the ability of lymphocytes to transform in response to phytohemagglutinin were studied in healthy volunteers undergoing prolonged enflurane or halothane anesthesia without coincident surgical operation. Anesthesia was associated with a modest leukocytosis that persisted into the first post-anesthesic day, primarily due to an influx of neutrophils into the circulation. There was no significant alteration, either during or following anesthesia, in the ability of the volunteers' lymphocytes to transform in response to phytohemagglutinin when compared with either preanesthetic values or unanesthetized controls. Depression of lymphocyte transformation does not appear to follow prolonged enflurane or halothane anesthesia in the absence of a surgical procedure.     

Comparison of lidocaine and saline for epidural top-up during combined spinal-epidural anesthesia in volunteers

This study was designed to determine the efficacy of saline as an epidural top-up to prolong spinal anesthesia during combined spinal-epidural anesthesia (CSEA). Eight volunteers received three separate CSEAs with intrathecal lidocaine (50 mg). After two-segment regression, each subject received either a saline (10 mL), lidocaine 1.5% (10 mL), or control sham (0.5 mL saline) epidural injection in a randomized, double-blind, triple cross-over fashion. Sensory block was assessed by pinprick and tolerance to transcutaneous electrical stimulation (TES) equivalent to surgical stimulation at the knee and ankle. Motor strength was assessed with iso-metric force dynamometry. Data were analyzed with a repeated measures analysis of variance and a paired t-test. Sensory block to pinprick was prolonged in the thoracolumbar dermatomes only by lidocaine (P < 0.05). Neither lidocaine nor saline prolonged the duration of tolerance to TES at the tested sites. Instead, saline decreased the duration of tolerance to TES by 20 and 24 min at the knee and ankle (P < 0.05). Recovery from motor block at the quadriceps was prolonged by an epidural injection of lidocaine (P < 0.05). We conclude that when 10 mL of epidural saline is administered after two-segment regression, it is an ineffective top-up and may decrease the duration of spinal anesthesia during CSEA.     

Pharmacokinetics of triptorelin after intravenous bolus administration in healthy males and in males with renal or hepatic insufficiency

PURPOSE: The aim of the present study was to validate a simple MRI-procedure for semiquantitative assessment of regional cerebral blood flow. MATERIALS AND METHODS: Unilateral cerebral ischaemia (30 minutes) in the territory of the middle cerebral artery was induced in 14 anesthetised rates. The MRI-experiment consisted in an intravenous bolus injection of gadolinium-DTPA, recording of the cerebral contrast kinetics with a T2*-weighted pulse sequence, and measurement of the maximal concentration change at a chosen reference point of time. To measure perfusion quantitatively, a microsphere technique, an accepted reference technique was used. With both methods a perfusion index related to the contralateral side was calculated. RESULTS: In all cases decreased perfusion was detected by the MRI technique. The perfusion indices correlated with a coefficient of correlation of r = 0.89 (p < 0.001). CONCLUSION: The results demonstrate that contrast-enhanced MRI with bolus injection can be implemented with clinical potential as a semiquantitative instrument for the assessment of cerebral perfusion. Regional cerebral blood volume and collateral blood flow may interfere with the estimate of blood flow.