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Biomedical subjects

M Leuwer

Publications and source records attributed to M Leuwer.

70 records · Page 4Linked to original sources
PubMed1998

Remifentanil, fentanyl, and alfentanil have no influence on the respiratory burst of human neutrophils in vitro.

BACKGROUND: Anaesthetic agents inhibit certain functions of human neutrophils. The respiratory burst (RB) enzyme in the plasma membrane of neutrophils leads to the production of superoxide anion. The oxygen radicals are responsible for killing phagocytised micro-organisms. We investigated the in vitro influence of remifentanil, fentanyl, and alfentanil on the respiratory burst of human neutrophils. METHODS: For the flow-cytometric evaluation, leukocytes were obtained as supernatant following sedimentation and were incubated with the tested drugs. The concentrations in vitro were adjusted to conform to the plasma concentrations reported for anaesthesia and also to 10-fold higher concentrations. The RB was measured by intracellular oxidation of dihydrorhodamine to fluorescent rhodamine after induction of phorbol-myristate-acetate (PMA), Escherichia coli (E. coli) or priming by tumour necrosis factor alpha followed by stimulation of n-formyl-methionyl-leucyl-phenylalanine (TNF-alpha/FMLP). In order to exclude prestimulation of the neutrophil granulocytes, negative controls were carried out. Propidium iodide (PI) was added for viability discrimination immediately prior to flow cytometry measurement. RESULTS: Regardless of the triggering agents chosen (PMA, E. coli, TNF-alpha/FMLP), remifentanil, fentanyl, and alfentanil had no significant effect on the neutrophils' respiratory burst even in concentrations which were higher than those encountered during in vivo conditions. CONCLUSION: With respect to peri- and postoperative risk of infection, anaesthetics and analgetics with no inhibiting effect on neutrophil function should be used. These results show that remifentanil, fentanyl, and alfentanil do not influence the neutrophils' respiratory burst in vitro.

Alfentanil↗
PubMed1997

Inhibition of neutrophil respiratory burst and chemotaxis in vitro by thiopentone but not methohexitone.

Administration of high-dose barbiturates may be used as an appropriate adjunctive treatment for control of intracranial pressure. The thiobarbiturate, thiopentone, has been reported to increase the rate of nosocomial pulmonary infection. This may be a substance-related effect of thiobarbiturates and it may be clinically important in barbiturate-sedated patients with severe head injury. Thus, the effects of the dose-response relationship of two commonly used barbiturates (thiopentone and methohexitone) on two vital aspects of neutrophil function were tested. We studied the production of superoxide anion during the respiratory burst by means of a flow cytometric method, and we assessed N-formyl-methionyleucylphenylalanine-induced neutrophil chemotaxis using the results produced by specific migration. The concentrations of thiopentone and methohexitone tested in vitro were adjusted to conform to the plasma concentrations reported for anesthesia and also to 10-fold higher concentrations. Only thiopentone dose dependently decreased respiratory burst and N-formyl-methionyleucylphenylalanine-induced chemotaxis. Methohexitone produced minimal effects in both concentrations. It was demonstrated that thiopentone had a direct effect on the intracellular respiratory burst oxidase enzyme system. The postulated free radical scavenging capacity of thiopentone was ruled out.

Journal Article↗
PubMed1997

[Intubation conditions and the development of neuromuscular blockade with rocuronium in endoscopic ORL surgery].

UNLABELLED: Rocuronium is a new nondepolarizing muscle relaxant for which a fast onset has been described. The goal of this study was to examine whether the characteristics of rocuronium could make it an appropriate relaxant for the anaesthetic management of operations of intermediate duration such as endoscopic upper airway surgery. These operations, which require the anaesthesiologist and surgeon to "share" the patient's airway, require good muscle relaxation for endotracheal intubation and placement of endoscopic instruments. In addition, the time course of neuromuscular blockade and its relation to the quality of intubating conditions were analysed. METHODS: The study was approved by the local ethics committee; 30 patients (ASA status 1-3) scheduled for elective endoscopic upper airway surgery were included after written informed consent. Exclusion criteria were suspected difficult intubating conditions, neuromuscular disease, or antibiotic therapy with aminoglycosides during the last 24 h. Anaesthesia was induced by propofol 2 mg/kg and alfentanil 1 mg after volume loading with 500 ml Ringer's lactate and preoxygenation, and was maintained by propofol infusion 5-8 mg/kg/h and repetitive alfentanil injections according to clinical needs. Endotracheal intubation was performed by a senior anaesthesiologist 90 s after injection of rocuronium 0.6 mg/kg (2 x ED95). Intubating conditions were graded 1 to 4 (1 = excellent, 2 = good, 3 = sufficient, 4 = inadequate). Acceleromyography was used for neuromuscular monitoring by means of the TOF-guard (organon Teknika/Biometer). The adduction movement of the thumb was measured by an acceleration transducer while stimulating the ulnar nerve at the wrist via surface electrodes in a supramaximal train-of-four (TOF) mode (2 Hz every 15 s). Twitch height and TOF ratio were documented during the course of neuromuscular blockade. Data are presented as mean +/- standard deviation. RESULTS: Patients were aged 37 to 64 years (mean 54 +/- 7). Intubating conditions were excellent in 17 cases and good in 7. In 2 cases intubating conditions were graded sufficient, as patients could be easily intubated but showed clear diaphragmatic movements at intubation. In 4 patients intubating conditions could not be judged, as a laryngoscopic view of the glottic structures was impossible for anatomic reasons. Neuromuscular block at intubation was 78 +/- 22%, onset time 152 +/- 62 s, clinical duration 30 +/- 8 min, and recovery index 11 +/- 4 min. The TOF ratio required 51 +/- 14 min to return to 0.7. CONCLUSIONS: Good to excellent intubating conditions can be expected 90 s after injection of rocuronium 0.6 mg/kg. Diaphragmatic reactions cannot be excluded. Complete relaxation of the adductor pollicis muscle is not necessary for endotracheal intubation. Intubation at a certain time interval, for example, 90 s after injection of rocuronium 0.6 mg/kg, can be recommended. Onset and recovery characteristics of rocuronium make it an appropriate relaxant for the anaesthetic management of operations of intermediate duration such as endoscopic upper airway surgery. Care should be given, however, to detect inadequate recovery of neuromuscular transmission, as there are considerable interindividual differences in recovery.

Adult↗
PubMed1997

[Effect of remifentanil on respiratory burst of human neutrophilic granulocytes in vitro].

Recovery chances for severely ill patients have been significantly improved by the progress of intensive care medicine. The success of any therapy, however, is still jeopardized by postoperative infections and septic complications. In the early stage of bacterial infections polymorphonuclear leukocytes (PMNL) play a decisive role. After PMNL activation, the production of oxygen radicals during the respiratory burst (RB) denature the phagocytosed micro-organisms. Remifentanil is a new opioid which has been safely administered to various patient groups and shows pharmacokinetic advantages in comparison to the already established opioids. As some intravenous anaesthetics can influence PMNL functions, we analysed, by flow cytometry, the in vitro influence of clinically relevant remifentanil concentrations on the respiratory burst. In our study remifentanil had no influence on the respiratory burst of human PMNL in vitro, regardless of the RB triggering agents chosen.

Analgesics, Opioid↗
PubMed1996

[Effect of halothane, enflurane and isoflurane on the pharmacodynamics of mivacurium in children].

INTRODUCTION AND OBJECTIVE: Mivacurium is a new non-depolarising muscle relaxant with a relatively rapid onset and short duration of action. In children, intravenous injection of 0.2 mg/kg produces satisfactory relaxation. Because inhalational anaesthetics have been found to enhance the potency of muscle relaxants we determined if onset or recovery times following mivacurium are influenced by inhalation of halothane (HAL), enflurane (ENF) or isoflurane (ISO). METHODS: After intramuscular induction, 36 surgical children (2-6 years, ASA I) were randomly assigned to inhale either HAL (n = 12); ENF (n = 12) or ISO (n = 12). The train-of four (TOF) response was determined electromyographically (Relaxograph, Datex) at 20-second time intervals. Following ten minutes of inhalation of either HAL, ENF or ISO (0,8; 1,2; 1,0 vol% respectively) in N2 O/O2 (2:1), 0.2 mg/kg of mivacurium was injected intravenously. Patients were intubated at maximal T1-suppression and the intubating conditions were judged according to a graded score. Upon recovery of T1 = 25%, six patients in each group were antagonised with 30 micrograms/kg of neostigmine and 15 micrograms/kg of atropine; the recovery indices were compared with those from non-antagonised patients. Differences between groups were tested with multifactorial analysis of variance (p < 0.05). RESULTS: Intubating conditions were graded as "excellent" or "good" in all patients but one who showed moderate breath holding following the tube passage. Onset times of mivacurium were not different between patients receiving HAL: 2.4 min +/- 0.52 (+/ SD); ENF: 2.4 min +/- 0.55 or ISO: 2.6 min +/- 0.68. Time to T1 = 25% was 7.6 min +/- 2.91 (HAL); 7.9 min +/- 1.55 (ENF) and 8.6 min +/- 2.30 (ISO). Recovery indices were not significantly different between groups. Total duration of action in non-antagonised patients was 13.0 min +/- 3.32 (HAL); 14.3 min +/- 4.01 (ENF) and 19.6 min +/- 5.17 (ISO), whereas antagonised duration of action was 13.4 min +/- 5.11 (HAL); 13.3 min +/- 1.97 (ENF) and 15.6 min +/- 4.25 (ISO). The shorter total duration of action in patients receiving neostigmine (average 0.5-2 minutes) was statistically insignificant. DISCUSSION AND CONCLUSION: Following injection of 0.2 mg/kg of mivacurium, no clinically relevant differences in onset or recovery times were found between children receiving halothane, enflurane or isoflurane. No differences in heart rate or blood pressure were found between groups. Compared to previous investigations with mivacurium, we noted a 30-60% longer mean onset time and a 30% shorter mean spontaneous recovery time. This may be explained by the lower mean age of our patients, which correlates with a relatively higher volume of distribution, resulting in lower plasma concentrations if the dose is calculated per kilogramme body weight. The reduction of the mean recovery time by 2 minutes following neostigmine injection seems to be clinically irrelevant. Similar to adult, a twofold ED95 produces satisfactory surgical muscle relaxation in children receiving mivacurium. Thus, its onset time is comparable to that of vecuronium or atracurium. The shorter duration of action offering a tighter control over relaxation may be of clinical advantage in this age group.

Adult↗
PubMed1996

Flow cytometry evaluation of the in vitro influence of four i.v. anaesthetics on respiratory burst of neutrophils.

Exposure of neutrophils to anaesthetic agents may alter their functional characteristics and in patients undergoing long-term sedation this may be clinically relevant. We have investigated the in vitro influence of propofol, thiopentone, methohexitone and midazolam on phorbol 12-myristate 13-acetate (PMA)-induced respiratory burst of neutrophils by the intracellular oxidative transformation of dihydrorhodamine-123 to the fluorescent dye rhodamine-123 via flow cytometry. We tested in vitro concentrations similar to sedating, anaesthetic, 10-fold sedating and 10-fold anaesthetic plasma concentrations. All drugs showed similar inhibition of respiratory burst at sedating concentrations (1-6%). At anaesthetic concentrations, propofol produced significantly higher mean inhibition (7.3%) compared with thiopentone (4.5%) and methohexitone (0.9%). At 10-fold anaesthetic concentrations inhibition of respiratory burst by propofol was almost complete (90.8%) and significantly higher than that by thiopentone (29.2%) and methohexitone (1.8%). Methohexitone and midazolam had only minimal effects at all concentrations. The effect of the solvent of propofol (10% Intralipid) was similar to that of propofol. Thus suppression of respiratory burst of neutrophils by propofol may be caused by this lipid carrier.

Anesthetics, Intravenous↗
PubMed1995

Dose-response, time-course of action and recovery of rocuronium bromide in children during halothane anaesthesia.

Two groups of children, aged 1-4 years (n = 28) and 5-10 years (n = 28), respectively, received at random one of four doses of rocuronium (0.12, 0.17, 0.22 or 0.27 mg kg-1). When maximum block was obtained, further rocuronium to a total dose of 0.5 mg kg-1 was given. At a spontaneous T1 recovery of 25% the block was reversed with atropine and neostigmine in half the patients. The remainder were allowed to recover spontaneously. There was no difference in potency in the two age groups. An ED50 of 0.2 mg kg-1 was estimated. The estimates of ED50 were model-dependent of approximately 0.32 mg kg-1. The maximum block was found significantly higher in the younger age group (99.0 +/- 1.5% (mean +/- SD)) as compared to the older group (97.5 +/- 2.3%), and the clinical duration was also longer (16.6 +/- 5.3 min vs. 13.3 +/- 3.8 min), respectively. There was no significant difference between the two age groups in duration90 (26.9 +/- 6.5 min, 22.5 +/- 6.7 min, respectively) and duration0.7 (27.6 +/- 6.0 min, 24.9 +/- 7.9 min, respectively). Recovery time25-75, recovery time25-90, but not recovery time25-0.7 were found significantly longer in the 1-4 year group as compared to the times in older children. Neostigmine administration reduced recovery time by approximately half to two-thirds. MAP was not influenced by rocuronium. Following the injection of rocuronium in the younger age group there was a 15% increase in heart rate compared to a 10% increase in the age group 5-10 years.

Androstanols↗
PubMed1994

Time course of action and recovery of rocuronium bromide in children during halothane anaesthesia--a preliminary report.

In this preliminary study, two groups of 15 patients, aged 1-4 years and 5-10 years respectively, received one of four doses of rocuronium (0.12, 0.17, 0.22 or 0.27 mg kg-1) and when block was maximal a supplementary dose to bring them all to a total of 0.5 mg kg-1. In half the patients, the block was reversed with atropine and neostigmine at a T1 recovery of 25%. The remainder were allowed to recover spontaneously. The total dose produced a block of 95-100% in all patients. The clinical duration of action was shorter under halothane anaesthesia in children (mean 15 min approximately) than has previously been reported in adults under intravenous anesthesia. Mean spontaneous recovery time from T1 25% to a train-of-four ratio of 0.7 was about 11 min. Neostigmine doubled the rate of recovery. There was a moderate increase in heart rate in the younger age range.

Androstanols↗
PubMed1992

[Fetal monitoring for anesthesiologists].

Several monitoring methods for the fetus are presented, the knowledge of which is appropriate for anesthesiologists active in the field of obstetrics. A distinction is made between external, indirect methods for monitoring when the amniotic sac is intact and internal, direct methods employed when the sac has ruptured. Particular emphasis is placed on cardiotocography (CTG), which is an obligatory method of routine monitoring during the late period of cervical dilatation and expulsion. It registers the reaction of fetal heart rate to parturition and labor, and represents a good indirect measure of both uteroplacental blood flow and fetal cardiac reserve. Criteria of evaluation for cardiotocograms are presented on the basis of guidelines elaborated by the Standard Committee on Cardiotocography (Chairman: Prof. Dr. H. Rüttgers). These enable the status of the fetus to be evaluated with differentiation. An inevitable sign of fetal well-being is a normal baseline with a rate between 120 and 160 beats/min, normal microfluctuation, and oscillations between 5 and 25/min with absent variable or late decelerations. Warning signs are restricted microfluctuation, elevated baseline, variable decelerations, and clinical passage of meconium. Suspicious signs are a baseline between 100-119 and 161-170 beats/min, respectively, decreased oscillation amplitude, and protracted decelerations over as much as 2 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[The effect of continuous arteriovenous hemofiltration on the pharmacokinetics of azlocillin in anuric patients].

The influence of continuous arteriovenous hemofiltration on the pharmacokinetics of azlocillin was examined in eight anuric intensive care patients, each of whom received a short infusion of 5.0 g azlocillin. Azlocillin concentrations in blood were measured simultaneously in the afferent and efferent loops of the amicon Dia 20 hemofilter and in the ultrafiltrate by means of an agar diffusion technique. Pharmacokinetic parameters were calculated by a computer program based on a two compartment model. We found that the elimination half-life of azlocillin ranged between 218.8 and 342.8 min, a result comparable to those of other investigators, who found similar elimination half-lives in anuric patients. During an observation period of 270 min, only 0.2-1.1% of the total dose of azlocillin was eliminated by way of the hemofilter. Apparently, continuous arteriovenous hemofiltration has no clinically relevant implications for the dosage or the dosage intervals of this antibiotic. On the other hand, azlocillin was taken up by the amicon Dia 20 hemofilter during the infusion. After the infusion was stopped the filter released azlocillin to blood and ultrafiltrate. The ratio of concentration in ultrafiltrate to plasma concentration in the afferent loop of the hemofilter was higher for about 45 min during the elimination phase than during the infusion. The volume of distribution was much larger (mean 28.5 l) than that found by other investigators. Therefore, the amicon-Dia 20 hemofilter seems to function as an additional distribution space.(ABSTRACT TRUNCATED AT 250 WORDS)

Anuria↗
PubMed1990

[Use of fentanyl for anesthesia induction in cesarean section. Pharmacokinetics and pharmacodynamics in mother and child].

A group of 36 patients in the last trimester of pregnancy and scheduled for cesarean section were examined during the induction of standardized general anesthesia (methohexitone 1.5 mg/kg, succinylcholine 1.5 mg/kg). No other inhalation anesthetics than N2O/O2 (50%:50%) were administered. In addition, 18 of the women received 0.005 mg/kg fentanyl prior to intubation. The remaining 18 patients served as a control group. In the study group maternal fentanyl plasma levels were determined 1 min after injection and again at the time of omphalotomy (radioimmunoassay). Immediately after clamping of the umbilical cord the fetal fentanyl plasma levels and the pH, pCO2 and pO2 values in both umbilical vein and artery were measured. The feto-maternal ratio and the fetal uptake were calculated. RESULTS. Maternal fentanyl plasma levels decreased significantly, from 7.84 (3.55-17.24) ng/ml 1 min after injection to 5.92 (2.01-14.15) ng/ml during omphalotomy. The corresponding fentanyl plasma levels in the umbilical vein were 2.08 (0.88-3.42) ng/ml. The feto-maternal ratio was 0.44 (0.08-1.00). The induction-delivery time ranged from 2 to 8 min. There was a significant correlation between umbilical-venous fentanyl concentration and the induction-delivery time: the longer the induction-delivery time the lower the fentanyl concentration in the umbilical vein. The 1-min Apgar score was 8 (5-9), the 5-min Apgar score 9 (8-10) and the 10-min Apgar score 10 (9-10) in neonates born to the fentanyl group. Only the 1-min Apgar score was significantly lower than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Repeated injection of atracurium for muscle relaxation in abdominal surgery].

21 patients selected for abdominal surgery received intravenously after initiation of neuroleptic analgesia for intubation, 0.5 mg/kg body weight (BW) of atracurium. Relaxation was maintained by repeat doses of 0.2 mg/kg BW atracurium. Both the time of intubation and the time of giving the repeat dose depended on the electromyographically measured stimulus response to supramaximal stimulation of the ulnar nerve (Datex-NTM, "Train-of-Four" stimulation). Intubation was effected at maximal inhibition of stimulus response, on the average after 195 +/- 90 sec. The duration of clinical efficacy was 33 +/- 8 min on the average, the recovery index 13 +/- 7 min and the duration of the full effect 54 +/- 6 min. The repeat doses were administered as soon as stimulus response recovered to 25% of the original value. Up to a cumulative total dose of 1.5 mg/kg BW atracurium no extension of the duration of clinical efficacy and of the full effect was seen, but there was a prolongation of the recovery index. The "Train-of-Four" quotient during recovery of relaxation was independent of the cumulative total dose. In the dosage levels described here, atracurium hardly exercised any action on pulse rate and blood pressure.

Abdomen↗
PubMedDate not supplied

In vitro influence of parenteral lipid emulsions on the respiratory burst of neutrophils.

The in vitro effect of a fish oil-derived lipid emulsion (omega-3) on the superoxide anion production during the respiratory burst (RB) of human neutrophils was compared to a LCT lipid (Intralipid), and an LCT/MCT emulsion (Lipofundin MCT). The effects of two concentrations (60 and 600 micrograms/mL) were evaluated by rhodamine in a flow cytometer. The RB was induced either by stimulation with Escherichia coli (E. coli) or by priming with TNF-alpha and FMLP stimulation. The results (mean +/- SD%, P < 0.05) were compared to positive control responses (RB without lipids). omega-3 (60 micrograms/mL, -8.2 [9.3]%; 600 micrograms/mL, -9.6 [11.1]%) and LCT (600 micrograms/mL, -8.0 [9.3]%) significantly suppressed the RB after stimulation with E. coli. LCT/MCT increased the RB after E. coli (60 micrograms/mL, 15.7 [15.4]%; 600 micrograms/mL, 42.7 [21.4]%) as well as after TNF-alpha/FMLP stimulation (600 micrograms/mL, 27.4 [23.7]%). The in vitro influence of parenteral lipid emulsions on the superoxide anion production of human neutrophils is dependent on the length of the fatty acid molecule.

Drug Combinations↗