[Anesthesia and hyperbilirubinemia].
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
P Conzen
Publications and source records attributed to P Conzen.
[Sevoflurane: metabolism and toxicity].
The new inhalational anesthetic sevoflurane is biotransformed by approximately 5%. Serum fluoride concentrations resulting from transformation mainly depend on rate of hepatic defluorination, total amount of anesthetic given and the solubility of the volatile anesthetic, as expressed by its blood gas partition coefficient. Enflurane is metabolized by 5-11%. However subsequent peak fluoride levels are lower than after sevoflurane which is a consequence of its lower rate of hepatic defluorination. To date numerous studies have examined the nephrotoxic potential of the sevoflurane degradation product fluoride. However, fluoride-related toxicity was not observed, neither in clinical or in animal studies, nor after prolonged administration or in patients with preexisting renal disease. New insights into intrarenal metabolisation of volatile anesthetics may well explain absence of nephrotoxicity after sevoflurane. The threshold of fluoride nephrotoxicity of 50 mumol/l, which has been empirically found after methoxyflurane, and which is still listed in many medical textbooks, can not be assumed a marker of nephrotoxicity after isoflurane, enflurane or sevoflurane. Therefore also, the elevated serum fluoride concentrations, as regularly obtained after anesthesia with sevoflurane are devoid of clinical significance. In addition, exposure to sevoflurane or its metabolites is not associated with hepatic toxicity.
Anesthetics, Inhalation↗
[Is halothane "out"?].
Explore the source record for details and available documents.
Anesthetics, Inhalation↗
[Water is for washing--but not only!].
Explore the source record for details and available documents.
Anesthesia↗
Enhancement of the leukocyte-endothelial cell interaction in collecting venules of skeletal muscle by protamine.
OBJECTIVE: A transient but severe systemic leukopenia regularly occurs after the antagonization of heparin by protamine in patients and in animals. The aim of the present study was to investigate the site and mechanisms of white blood cell retention during this transient leukopenia by studying the leukocyte-endothelial cell interaction in skeletal muscle venules. METHODS: Syrian golden hamsters were equipped with a dorsal skinfold chamber for intravital fluorescence microscopy and arterial and venous catheters for drug infusion, blood pressure measurement, and blood sampling. Microhemodynamic parameters and leukocyte-endothelial cell interactions were observed in one single collecting venule per animal after intravenous infusion of saline solution (control, n = 10), of protamine (n = 9), and after infusion of heparin followed by either intravenous protamine (n = 9) or intraarterial protamine (n = 9). RESULTS: All parameters remained unchanged in the control group. Whereas venular diameters remained unchanged, protamine transiently increased arterial blood pressure and venular erythrocyte velocity in all groups. Systemic leukocyte counts and the venular leukocyte discharge concentration decreased concurrently after protamine administration by about 60% to 70% at 2 minutes while the fraction of rolling leukocytes and the number of adherent leukocytes remained unchanged. Two and one-half minutes later, systemic leukocyte counts and venular discharge concentrations normalized while the fraction of leukocytes rolling slowly along or adhering firmly to the venular endothelial wall increased considerably and similarly in all groups receiving protamine. Myeloperoxidase (an indicator of polymorphonuclear leukocytes) determination in 20 separate hamsters 2 minutes after protamine infusion revealed increased myeloperoxidase activity exclusively in the lungs. CONCLUSION: The response of leukocytes to protamine infusion with or without prior heparinization is biphasic: initial retention of leukocytes in the lungs is followed by enhanced leukocyte-endothelial cell interaction in the systemic circulation.
Animals↗
Comparison of sevoflurane/fentanyl and isoflurane/fentanyl during elective coronary artery bypass surgery. Sevoflurane Venture Group.
PURPOSE: Due to the progressive aging of the surgical population, the proportion of patients with coronary artery disease (CAD) is likely to increase. The effects of the new inhalational anaesthetic sevoflurane must be determined in patients with known CAD. METHODS: This multicentre, randomized, open-label study compared the haemodynamic and cardiovascular effects of sevoflurane and isoflurane with fentanyl in 284 ASA physical status II-IV patients undergoing elective coronary artery bypass graft (CABG). RESULTS: Satisfactory records were available in 272 patients, 139 sevoflurane (Group S) and 133 isoflurane (Group I). There were no differences between groups for demographic data except that more patients in Group S were taking preoperative beta-blockers (P = 0.03). The mean end-tidal MAC and MAC.hr requirements between groups were not different (Group S received 0.63 +/- 0.02 MAC and 1.00 +/- 0.05 MAC. hr while Group I received 0.58 +/- 0.02 MAC and 0.92 +/- 0.05 MAC. hr P = NS). The preCPB use of intravenous fentanyl was not different between groups. There was a similar decrease in haemodynamic variables in both groups after induction that persisted throughout the preCPB period. The incidence of preCPB myocardial ischaemia, adverse haemodynamic events and use of vasoactive drugs did not differ between groups. The incidence of postoperative myocardial infarction was 2.2% for Group S and Group I was 4.5% (P = NS). There were five postoperative deaths, one of which was attributed to a cardiac cause (Group I). CONCLUSION: In patients undergoing elective CABG with low risk factors, either sevoflurane or isoflurane, combined with fentanyl, provided an acceptable preCPB haemodynamic profile and cardiac outcomes.
Aged↗
[Awakening from anesthesia and recovery of cognitive function after desflurane or isoflurane].
UNLABELLED: Desflurane is a new volatile anaesthetic with an extremely low blood/gas partition coefficient of 0.42. This should provide a rapid recovery from anaesthesia. METHODS: We studied 100 adult patients, ASA class I or II, undergoing elective orthopaedic surgery randomly assigned to anaesthesia with desflurane (n = 50) or isoflurane (n = 50) supplemented by nitrous oxide in oxygen. Clorazepat was given for premedication, fentanyl and thiopental for induction of anaesthesia, followed by maintenance with desflurane or isoflurane as clinically appropriate. Emergence from anaesthesia was measured as well as return of cognitive functions (extended Aldrete score, digit symbol substitution test, and visual analogue scales [VAS]). RESULTS: While the demographic characteristics and administrated doses of fentanyl and thiopental were comparable, the recovery profiles in both groups were different. After discontinuation of the volatile anaesthetics, times to extubation and ability to follow simple commands were significantly shorter after desflurane than after isoflurane. Extended Aldrete scores, estimation of the patients' physical condition, results of the digit symbol substitution test, measuring cognitive functions, and rates of drowsiness and weakness on VAS showed better recovery with less impairment of cognitive function in the desflurane group than in isoflurane patients even 120 min after anaesthesia. VAS pain scores and doses of analgesic drugs given within the first 2 postoperative hours, however, showed no significant differences. Desflurane patients were also judged fit for discharge from the recovery room significantly faster. CONCLUSIONS: Our results demonstrate that desflurane anaesthesia, even when supplemented by premedication, intraoperative opioids, and nitrous oxide may offer clinical advantages over isoflurane as far as the post-anaesthetic recovery profile is concerned.
Adult↗
[Hemodynamic effects of three different dosages of the induction hypnotic, eltanolone, in coronary surgery patients].
UNLABELLED: Eltanolone is a new steroid anaesthetic agent that is 5-beta reduced derivative of progesterone. In the present study we investigated the haemodynamic effects of eltanolone or thiopentone in patients scheduled for coronary artery bypass grafting. METHODS: After obtaining approval of the institutional ethics committee and informed patient consent, 40 patients (age 45-70 years, ASA III and IV, ejection fraction > 50%, cardiac index > 2.5 l/min per m2) were randomly assigned to four groups, each containing 10 patients: After premedication with 2 mg flunitrazepam, anaesthesia was induced with 3 mg/kg thiopentone in group 1, 0.5 mg/kg eltanolone in group 2, 0.75 mg/kg eltanolone in group 3, 1.0 mg/kg eltanolone in group 4. Each patient additionally received 3 mirograms/kg fentanyl after induction and 0.1 mg/kg pancuronium. Heart rate, mean arterial pressure, pulmonary arterial pressure, central venous pressure, pulmonary artery occlusion pressure and cardiac output were recorded in the awake state, 2 min after induction of anaesthesia, and 1 and 5 min after intubation. Cardiac index and systemic vascular resistance were calculated. RESULTS: Two minutes after induction, mean arterial pressure was significantly lower than the baseline (P < 0.05) in each group. Mean arterial pressure changes were more prominent in the case of eltanolone, but intergroup tests did not reveal significant differences between the four groups. There was a fall in cardiac index in all groups, and these changes reached the level of significance only in the thiopentone patients. The most obvious difference between eltanolone and thiopentone was systemic vascular resistance. It dropped significantly 2 min after induction with eltanolone at all dosages. In contrast, there was an increase in systemic vascular resistance following induction of anaesthesia with thiopentone. Intergroup tests also showed significantly (P < 0.05) lower systemic vascular resistance 1 and 5 min after intubation with eltanolone compared to thiopentone. DISCUSSION: Mean arterial pressure reduction induced by eltanolone is most likely the result of the combination of a decrease in cardiac contractility and peripheral vasodilatation. In contrast, mean arterial pressure reduction in the case of thiopentone seems to be exclusively related to the negative inotropic properties of the drug. Results of a dosage finding study [5] with eltanolone revealed an AD50 of 0.33 mg/kg. In our study 0.5 mg/kg eltanolone brought all the patients to sleep within 2 minutes. The haemodynamic results do not show any significant difference up to twofold dosage. Therefore, the therapeutic margin seems to be large. Because of considerable interindividual variability additional studies in larger collectives are required for definitive evaluation of the drug.
Aged↗
[New inhalation anesthetics].
Recently, two new halogenated volatile anaesthetics, sevoflurane and desflurane, have been approved for clinical use in Germany. Their low solubility in blood is the most important common property, and this represents the most obvious difference from the inhalational anaesthetics currently used. Extensive clinical and experimental evaluations have confirmed the superior pharmacokinetic properties predicted. Both sevoflurane and desflurane provide more rapid emergence from anaesthesia, permit easier titration of the anaesthetic dose during maintenance and offer more rapid recovery from anaesthesia. For sevoflurane, there are additional advantages: a pleasant odor, negligible airway irritation, and excellent pharmacodynamic characteristics that even provide cardiovascular stability comparable to isoflurane. A certain disadvantage and source of potential nephrotoxicity result from the metabolism of sevoflurane (2-5%) to anorganic fluoride and degradation to compound A in carbon dioxide absorbents. The extensive clinical data reported to date have revealed no evidence that sevoflurane has adverse renal effects. New insight into the pathomechanism of nephrotoxicity associated with either production of fluoride or compound A may well support clinical experience. Desflurane strongly resists in vivo metabolism and because of this it appears to be devoid of toxicity. Nevertheless, potential side-effects may result from degradation in dry absorbents and subsequent release of CO, from its extreme pungency and irritating airway effects. Thus, desflurane is not recommended for induction of anaesthesia, especially in children. The tendency for desflurane transiently to stimulate sympathetic activity, especially at concentrations above 1.0 MAC, limits its application in patients with cardiac disease.
Anesthesia, Inhalation↗
Midlatency auditory evoked potentials during anaesthesia with increasing endexpiratory concentrations of desflurane.
BACKGROUND: Under general anaesthesia with the volatile anaesthetics halothane, enflurane and isoflurane, midlatency auditory evoked potentials (MLAEP) are suppressed dose-dependently. Therefore, MLAEP have been used to measure depth of anaesthesia and to indicate intraoperative awareness. Desflurane is a new volatile anaesthetic and its effect on MLAEP have not been studied previously. METHODS: We have studied MLAEP during general anaesthesia with increasing endexpiratory concentrations of desflurane in 12 patients scheduled for elective gynaecological surgery. Auditory evoked potentials were recorded in the awake state and during anaesthesia with endexpiratory steady state concentrations of 1.5, 3.0, 4.5 and 6.0 vol % of desflurane on vertex (positive) and mastoids on both sides (negative). Latencies of the peaks V, Na, Pa, Nb, Pl (ms) and amplitudes Na/Pa, Pa/Nb and Nb/Pl (micro V) were measured. RESULTS: In the awake state, MLAEP had high peak-to-peak amplitudes and a periodic waveform. During general anaesthesia with increasing endexpiratory concentration of desflurane, the latency of the brainstem response V increased only slightly. In contrast, MLAEP showed a marked dose-dependent and statistically significant increase in latencies of Na, Pa, Nb and Pl and decrease in amplitudes of Na/Pa, Pa/Nb and Nb/Pl. Under 6.0 vol % of desflurane MLAEP were severely attenuated or even abolished. CONCLUSION: Based on these observations, endexpiratory concentrations of > or = 4.5 vol % desflurane should suppress awareness phenomena such as auditory perceptions during anaesthesia.
Adult↗
[Toxicology and clinical significance of base-catalized degradation of sevoflurane to Compound A].
Sevoflurane breaks down in basic environments to form a vinyl ether known as Compound A. This compound is toxic in the rat, with an LC50 of about 400 ppm after 3 h exposure and with renal damage evident between 50 and 100 ppm. There is no valid current evidence that Compound A is toxic in man, and the rat may not be an appropriate model for determination of this breakdown product's toxic potential in humans. The main factors influencing the degree of patient exposure to Compound A include fresh gas flow, sevoflurane concentrations, absorber temperature and composition, and the patient's carbon dioxide production.
Anesthetics, Inhalation↗
[Fluoride-induced nephrotoxicity: factor fiction?].
In the 1960s, the widespread use of the inhalational anaesthetic methoxyflurane was associated with a significant occurrence of postoperative renal dysfunction. This was attributed to hepatic biotransformation of methoxyflurane and subsequent release of inorganic fluoride ions into the circulation. Based upon the clinical experience with methoxyflurane, serum fluoride concentrations exceeding 50 mumol/l were considered to be nephrotoxic. Without further reevaluation, this 50 mumol/l threshold was subsequently applied to other fluorinated anaesthetics as well. Enflurane and even isoflurane may, when used during prolonged operations, also yield anorganic fluoride levels in excess of 50 mumol/l. Nevertheless, no cases of renal dysfunction attributable to prolonged use of these anesthetics have been reported. About 4% of the new inhalational anaesthetic sevoflurane is metabolized, and fluoride concentrations exceeding those after enflurane are frequently measured. Numerous studies have examined the nephrotoxic potential of sevoflurane degradation products. However, fluoride-related toxicity has been observed neither in animal nor in clinical studies, including prolonged administration and patients with pre-existing renal disease. New insights into the intrarenal metabolisation of volatile anaesthetics may well explain the absence of nephrotoxicity after sevoflurane. The threshold for fluoride nephrotoxicity of 50 mumol/l, still given in many medical text-books, can no longer be applied as an indicator of nephrotoxicity after isoflurane, enflurane or sevoflurane. Therefore, the elevated serum fluoride concentrations consistently recorded following anaesthesia with sevoflurane are devoid of clinical significance.
Anesthetics, Inhalation↗
[Intraoperative awareness and auditory evoked potentials].
Midlatency auditory evoked potentials (MLAEP) are suppressed dose-dependently during anaesthesia with a variety of general anaesthetics. Therefore, MLAEP have been proposed to measure depth of anaesthesia and to indicate intraoperative awareness. Several studies give evidence of a close relationship between MLAEP and motor signs of wakefulness, intraoperative awareness, and explicit and implicit memory functions during general anaesthesia. Summarising these data, one may conclude that there is a close hierarchical relation between cognitive function, memory and wakefulness during anaesthesia, and MLAEP latencies. A short Nb latency below 45 ms is consistent with conscious awareness and unimpaired memory function with explicit recall and adequate response to commands. When Nb latency increases to 45-50 ms, it may be associated with conscious awareness. Patients still respond to commands, but memory formation is impaired and explicit recall is lost. A further increase of Nb latencies seems to be consistent with unconscious awareness, characterised by implicit memory of intraoperative events; 60 ms seems to be the threshold value for motor signs of wakefulness during anaesthesia. With a further increase of MLAEP latency during anaesthesia, conscious awareness and memory formation, explicit and implicit recall, response to commands, and spontaneous purposeful movements during anaesthesia are blocked. The new volatile anaesthetic sevoflurane leads to a dose-dependent increase in MLAEP peak latencies and a decrease in MLAEP amplitudes. At about 1.5 vol.% end-expiratory sevoflurane concentration, MLAEP are significantly suppressed and Nb latency is in the range of 68-80 ms. Therefore, from the present data and those from the literature, one may expect that sevoflurane at concentrations greater than 1.5 vol.% for general anaesthesia would be able to suppress awareness phenomena such as purposeful movements, auditory perception, intraoperative wakefulness and awareness, memory formation, and explicit and implicit recall of intraoperative events.
Anesthetics, Inhalation↗
Does nitrous oxide affect coronary microcirculation? An intravital microscopic study in the canine heart.
The safe use of nitrous oxide, in particular in patients with coronary artery disease, has been questioned. This study was designed to determine whether nitrous oxide directly affects global coronary hemodynamic variables and coronary arteriolar microvessels in the absence of changes of myocardial oxygen consumption. In dogs the effects of nitrous oxide were evaluated during normotension (NT, intravenous [IV] piritramid, nitrogen/oxygen; and NT/N2O, IV piritramid, nitrous oxide/oxygen) and during hypotension (MAP 60 mm Hg) (HT, IV piritramid, halothane, nitrogen/oxygen; and HT/N2O, IV piritramid, halothane, nitrous oxide/oxygen). The diameter of coronary arteriolar microvessels (range, 20-450 microns) was assessed by intravital fluorescence microscopy. Myocardial blood flow was determined by radioactive microspheres. Systemic and coronary hemodynamics, as well as arteriolar microvessel diameters, were comparable between NT and NT/N2O. During HT, nitrous oxide (HT/N2O) affected neither systemic nor coronary hemodynamics. Moreover, there was no obvious difference in the diameters of coronary microvessels between HT and HT/N2O. In conclusion, nitrous oxide, whether at normotensive or hypotensive conditions, neither influences coronary arteriolar tone nor reduces or redistributes myocardial blood flow.
Animals↗
Hemodynamic effects of anesthetic induction with eltanolone-fentanyl versus thiopental-fentanyl in coronary artery bypass patients.
We evaluated the hemodynamic profile of eltanolone and fentanyl versus thiopental and fentanyl anesthetic induction in patients with documented coronary artery disease. Fifty patients scheduled for coronary artery bypass grafting were randomly assigned to two treatment groups (25 patients each). Anesthesia was induced by eltanolone (0.5 mg/kg) or by thiopental (3 mg/kg). Each patient also received 3 micrograms/kg fentanyl and 0.1 mg/kg vecuronium. Heart rate, arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures, and cardiac output were determined in the awake state, 2 min after induction of anesthesia, and at 1 and 5 min after intubation, which was performed 3 min after induction. Between-group statistics showed significantly (P < 0.05) lower mean arterial pressure and systemic vascular resistance for eltanolone-treated patients at all measuring points. Pulmonary capillary wedge pressure was lower at 1 min after intubation; left ventricular stroke work index was lower at 1 and 5 min after intubation in the eltanolone group. We conclude that the lower mean arterial pressure with eltanolone as compared to thiopental is a result of greater peripheral vasodilation.
Adult↗
The effects of anesthesia with increasing end-expiratory concentrations of sevoflurane on midlatency auditory evoked potentials.
We studied midlatency auditory evoked potentials (MLAEP) during general anesthesia with increasing end-expiratory concentrations of sevoflurane in 12 patients scheduled for elective gynecologic surgery. After oral premedication with 20 mg clorazepate dipotassium, anesthesia was induced with etomidate (0.2 mg/kg intravenously [IV]). Vecuronium (0.1 mg/kg) was given for neuromuscular block, and controlled ventilation with sevoflurane in 100% O2 was instituted. Auditory evoked potentials were recorded in the awake state and during anesthesia with end-expiratory steady-state concentrations of 0.5, 1.0, 1.5, and 2.0 vol% of sevoflurane on vertex (positive) and mastoids on both sides (negative). Latencies of peaks V, Na, Pa, Nb, and P1 (ms) and amplitudes of Na/Pa, Pa/Nb, and Nb/P1 (microV) were measured. In the awake state, MLAEP had high peak-to-peak amplitudes and a periodic waveform. During general anesthesia with increasing end-expiratory concentrations of sevoflurane, the latency of the brainstem response V increased slightly. In contrast, MLAEP showed marked dose-dependent, statistically significant increases in the latencies of Na, Pa, Nb, and P1 and decreases in the amplitudes of Na/Pa, Pa/Nb, and Nb/P1. Under 2 vol% of sevoflurane, MLAEPs were severely attenuated or abolished. Based on these observations, > or = 1.5 vol% sevoflurane should suppress phenomena such as auditory perceptions, intraoperative wakefulness, and awareness.
Adult↗
Inhalation anaesthesia at the extremes of age: geriatric anaesthesia.
No single anaesthetic technique is superior for all elderly patients, although the prognosis is improved if minor surgical procedures are performed with local anaesthesia rather than with general or major regional anaesthesia. If general anaesthesia is required, which specific inhalation anaesthetic can improve the prognosis of the geriatric patient? The low solubility of desflurane and its resistance to biodegradation would seem to recommend its use in the geriatric patient. However, these theoretical advantages remain to be adequately documented.
Aged↗
[New aspects of pain research and therapy and inhalation anesthetics].
Explore the source record for details and available documents.
Anesthesiology↗