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Biomedical subjects

E Kochs

Publications and source records attributed to E Kochs.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Ketamine racemate and S-(+)-ketamine. Cerebrovascular effects and neuroprotection following focal ischemia].

The phencyclidine derivative ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist with the thalamo-neocortical projection system as the primary site of action. Racemic ketamine consists of the enantiomers S(+)-ketamine and R(-)-ketamine. Racemic ketamine has never been considered an adequate anaesthetic agent in neurosurgical patients since it produces regionally specific stimulation of cerebral metabolism (CMRO2) and increases cerebral blood flow (CBF) and intracranial pressure (ICP). However, recent experiments suggest that both tracemic ketamine and S(+)-ketamine may reduce infarct size in animal models of incomplete cerebral ischaemia and brain injury. This experimental protective effect appears to be related to decreases in Ca++ influx and maintenance of brain tissue magnesium levels due to NMDA and quisqualate receptor blockade by ketamine. Studies in dogs have shown that racemic ketamine (2.0 mg/kg) increases CBF in the presence of the cerebral vasodilator N2O. In contrast, studies in rats without background anaesthesia showed increases in CBF after racemic ketamine (100 mg/kg i.p.). This suggests that the cerebrovascular effects of racemic ketamine are related to the pre-existing cerebrovascular tone induced by background anaesthetics. Cerebrovascular CO2 reactivity was maintained regardless of the baseline cerebrovascular resistance. There are several mechanisms by which racemic ketamine may increase CBF. It induces dose-dependent respiratory depression with consequent mild hypercapnia in spontaneously ventilating subjects. This produces vasodilation due to the intact cerebrovascular CO2 reactivity. Racemic ketamine also induces regional neuroexcitation, which leads to stimulation of cerebral glucose consumption in the limbic, extrapyramidal, auditory, and sensory-motor systems. This regional neuroexcitation with increased CMRO2 produces increases in CBF that can be blocked by infusion of barbiturates or benzodiazepines. However, increases in CBF with racemic ketamine (1 mg/kg) may also occur during normocapnia and without changes in CMRO2. This effect is related to some additional direct cerebral vasodilating potency of racemic ketamine based on a mechanism involving blockade of Ca++ channels. The effects of racemic ketamine on CBF autoregulation have not been investigated systematically. However, studies in rats have shown that CBF autoregulation was maintained with low- and high-dose S(+)-ketamine. Infusion of racemic ketamine alters intracranial volume and ICP. Studies in spontaneously ventilating pigs with and without intracranial hypertension have shown that racemic ketamine (0.5-5.0 mg/kg) produces increases in PaCO2 and ICP. In contrast, identical experiments with mechanical ventilation and controlled PaCO2 showed no changes in ICP following racemic ketamine infusion. This implies that increases in ICP are related to inadequate ventilation with consecutive hypercapnia and increases in intracranial blood volume. However, mechanical ventilation may not be sufficient to control ICP following racemic ketamine. Experiments in mechanically ventilated dogs indicate that racemic ketamine (2 mg/kg) increases cerebral blood volume and ICP even in the presence of normoventilation, a response that is reversible by hyperventilation or the administration of diazepam. Studies in patients have shown that racemic ketamine (2.0 mg/kg) reduces CBF in the presence of cerebral vasodilators like halothane or N2O. In contrast, studies in unanaesthetised humans showed increases in CBF after racemic ketamine (2-3 mg/kg). This observation is consistent with animal studies and suggests that the cerebrovascular effects of racemic ketamine are related to the pre-existing cerebrovascular tone induced by background anaesthetics. Studies in humans with and without intracranial pathology confirm the data from animal experiments. (ABSTRACT TRUNCATED)

Animals↗
PubMed1997

Haemodynamic changes and skeletal muscle oxygen tension during complete blood exchange with ultrapurified polymerized bovine haemoglobin.

OBJECTIVE: The study investigates the effect of continuous blood exchange with ultrapurified, polymerized bovine haemoglobin (UPBH) in comparison to hetastarch on haemodynamics, oxygen transport and skeletal muscle oxygen tension in a canine model. DESIGN: Sixteen anaesthetized beagle dogs underwent haemodilution with lactated Ringer's to a starting haematocrit of 20% followed by progressive blood exchange with 6% hetastarch 200,000/0.5 (HES, group 1) or UPBH (haemoglobin 13 +/- 1 g.dl-1, molecular weight (MW) 32-500,000, group 2) to haematocrit target levels of 15%, 10% and 5% or less. MEASUREMENTS AND RESULTS: Besides haemodynamics, skeletal muscle tissue oxygen tension (tPO2) was measured using a polarographic needle probe. In HES-treated animals, heart rate, cardiac output and blood flow were higher while systemic vascular resistance, systemic and regional arterio-venous oxygen difference (avDO2) and oxygen extraction ratios were lower when compared to the UPBH group. In spite of a higher final haematocrit of 5% in group 1, in comparison to group 2 with 2%, final muscular oxygen uptake (4.7 +/- 4 vs 10.1 +/- 2 ml.min-1) and mean tPO2 (11.8 +/- 2.3 vs 51.1 +/- 2.9 mm Hg) were lower in group 1 than in group 2. While tPO2 histograms were continuously shifted to lower oxygen tensions during progressive haemodilution with HES, UPBH-exchanged animals showed tPO2 histograms shifted to higher values than baseline. CONCLUSION: In spite of vasoconstriction, UPBH provided more haemodynamic stability and enhanced skeletal muscle tPO2 during progressive blood exchange when compared to HES.

Analysis of Variance↗
PubMed1997

[Intraoperative pain stimuli change somatosensory evoked potentials, but not auditory evoked potentials during isoflurane/nitrous oxide anesthesia].

PURPOSE: Evoked potentials are used for intraoperative monitoring to assess changes of cerebral function. This prospective randomised study assesses the influence of surgical stimulation on midlatency components of somatosensory (SEPs) and auditory evoked potentials (AEPs) in anaesthetised patients. METHODS: After approval of the Ethics Committee and written informed consent 36 orthopaedic patients (34 +/- 15 y, 73 +/- 14 kg. 1.71 +/- 0.07 m, ASA I-II) were randomly included in the study. Anaesthesia was induced with 1.5 micrograms/kg fentanyl, 0.3 mg/kg etomidate and 0.1 mg/kg vecuronium. The lungs were intubated and patients normoventilated in steady state anaesthesia with isoflurane (end-tidal 0.6%) and 66% nitrous oxide. 18 patients (group 1) were assigned to the SEP group: median nerve stimulation, recording at Erb, C 6 and the contralateral somatosensory cortex (N20, P25, N35) vs Fz. AEPs were recorded in group 2 (n = 18): binaural stimulation, recording at Cz versus linked mastoid (V, Na, Pa, Nb). Recordings were performed during 30 min before the start of surgery (baseline: BL), at skin incision (SURG1) and at the preparation of the periost (SURG2). Heart rate, mean arterial blood pressure, oxygen saturation, endtidal pCO2 and isoflurane (PetISO) concentrations were registered simultaneously. Data were analysed by one-way analysis of variance. Post hoc comparison were made by Mann-Whitney U-Wilcoxon Rank Sum Test with p < 0.05 significant. RESULTS AND DISCUSSION: During steady state isoflurane anaesthesia surgical stimulation (SURG2) resulted in significant increases of N20 P25 amplitudes compared with BL (BL: 1.4 +/- 0.7 microV; SURG2: 2.0 +/- 0.8 microV; p < 0.05). Latencies of SEPs and midlatency components of AEPs did not change over time. There were no differences in autonomic parameters between SEP and AEP groups. MAP increased from 76 +/- 6 mmHg at BL to 93 +/- 16 mmHg at SURG1 and 96 +/- 17 mmHg at SURG2 (n = 36; p < 0.05). HR increased from BL (60 +/- 8 beats/min) to SURG2 (76 +/- 12 beats/min). Increases of amplitudes of midlatency SEP amplitudes indicate increased nociceptive signal transmission which is not blunted by isoflurane-nitrous oxide anaesthesia. In contrast, unchanged AEPs indicate adequate levels of the hypnotic components of anaesthesia.

Adult↗
PubMed1997

[Effect of S-(+)-ketamine on autoregulation of cerebral blood flow].

PURPOSE: The present study investigates the effects of S-(+)-ketamine on cerebral blood flow (CBF) autoregulation in rats. METHODS: Following IRB approval, 24 nonfasted male Sprague-Dawley rats were anesthetised with isoflurane, intubated and mechanically ventilated. Catheters were inserted into the right femoral artery, both femoral veins, and into the right jugular vein for drug administration, measurement of mean arterial blood pressure (MAP), and blood sampling. Cortical cerebral blood flow was measured using laser-Doppler-flowmetry (PF 403, Perimed). At the end of surgery isoflurane was discontinued and all animals were randomly assigned to one of the following anaesthetic treatments. In group 1 (n = 8, control), anaesthesia was maintained using fentanyl (10 micrograms/kg i.v. bolus, followed by 25 micrograms/kg/h i.v.) and N2O/O2 (FiO2: 0.3). In group 2 (n = 8) and group 3 (n = 8) animals received 0.5 mg/kg/min S-(+)-ketamine i.v. or 1.0 mg/kg/min S-(+)-ketamine i.v. and O2/air (FiO2: 0.3), respectively. CBF was tested by graded haemorrhage. Arterial blood gases, arterial pH, and pericranial temperature were controlled over time. RESULTS: CBF autoregulation was maintained under low and high doses of S-(+)-ketamine compared to fentanyl/N2O-anaesthetised controls. However, low-dose S-(+)-ketamine shifted the autoregulatory curve towards higher MAP values. CONCLUSIONS: The present study indicates that autoregulatory cerebrovascular dilation is preserved with low and high doses of S-(+)-ketamine. Differences in the lower limit of CBF autoregulation may be consistent with an increased sympathetic tone induced by low doses of S-(+)-ketamine.

Anesthetics, Dissociative↗
PubMed1997

Interaction of midazolam with the nicotinic acetylcholine receptor of mouse myotubes.

The effects of midazolam on the peripheral embryonic nicotinergic acetylcholine receptor (nAChR) of mouse myotubes were studied to elucidate the mechanism of its effect on neuromuscular transmission. Standard patch clamp techniques on outside-out patches were used. Pulses of 10(-4) M acetylcholine (ACh) applied by a liquid filament switch technique elicited macroscopic channel currents with a peak current amplitude of approximately 40 pA within <1 ms. The current decayed with a time constant of 30-100 ms due to desensitization. When midazolam was added in stepwise increased concentrations (10(-7) M to 7 x 10(-4) M) to the pulses, the current decay became bi-exponential, and a concentration-dependent decrease of the fast component of decay was observed. The current amplitude, however, was reduced slightly, and only at high concentrations of midazolam. This may indicate that midazolam binds to the open channel to cause the block. The rate constant of block (b(+1)) was found to be 1.8 x 10(6) M/s. Recovery experiments revealed a rate of unblocking (b(-1)) of approximately 2 x 10(-1) s(-1). After preincubation of the patches with midazolam, a substantial reduction of the current amplitude was seen at very low midazolam concentrations (<10(-7) M), which suggests an additional closed channel block with a Kd of approximately 10(-6) M. This closed channel block may be responsible for the muscle-relaxing effects of midazolam.

Acetylcholine↗
PubMed1997

Isoflurane and sevoflurane interact with the nicotinic acetylcholine receptor channels in micromolar concentrations.

BACKGROUND: This study was performed to elucidate and compare the effects of sevoflurane and of isoflurane on the nicotinic acetylcholine receptor of mouse myotubes. The experiments were done with special reference to anesthetic concentrations considerably less than those used for clinical anesthesia. METHODS: The patch-clamp technique was used to record acetylcholine-activated currents from the embryonic type of the nicotinic acetylcholine receptor in the outside-out mode. A piezo-driven liquid filament switch was used for the ultrafast application of acetylcholine alone or in combination with isoflurane or sevoflurane. In addition, the patches were preexposed to either anesthetic, preceding the activation with acetylcholine. RESULTS: The current elicited by acetylcholine was reduced reversibly and in a concentration-dependent manner by both anesthetics, which were equally effective. Preexposure of the patches to isoflurane or sevoflurane showed an additional inhibition that was present at micromolar concentrations. The time courses of current decay could be fitted by single exponentials for isoflurane. At higher concentrations of sevoflurane, the current decay became biexponential. In contrast to isoflurane, sevoflurane increased the time constants of desensitization when applied in low concentrations. CONCLUSIONS: At the nicotinic acetylcholine receptor, isoflurane and sevoflurane act primarily through the same mechanisms: Both affect the open and the closed state of the channels in concentrations equal to and less than those encountered clinically. The kinetics of desensitization, however, are altered in a different manner. Thus there may be several different sites of interaction.

Anesthetics, Inhalation↗
PubMed1997

Topographical analysis of the EEG effects of a subconvulsive dose of lidocaine in healthy volunteers.

BACKGROUND: The purpose of the present study was to assess the effects of intravenous lidocaine on spatial changes of electroencephalographic power and on psychomotoric status in conscious volunteers. METHODS: In 11 healthy volunteers lidocaine (2-min bolus, 100 mg; 15 min infusion, 40 micrograms.kg-1.min-1) or placebo were given intravenously in a randomized, single-blinded, two-way crossover study. Haemodynamics and lidocaine plasma concentrations were measured at baseline and within a period of 30 min following bolus injection. Vigilance and emotional status were tested using visual analogue scales (VAS). Toxic CNS effects were evaluated by a questionnaire. The raw EEG (17 leads, reference Cz) and computed power spectra were continuously recorded. RESULTS: The chosen lidocaine dosage led to nearly constant plasma concentrations (unbound lidocaine 2.5 min and 15 min after bolus 0.36 +/- 0.14 microgram/ml and 0.30 +/- 0.06 microgram/ml, respectively [mean +/- SD]). The placebo caused no symptoms, changes in VAS-scores or EEG-parameters. Lidocaine induced pronounced subjective symptoms and significant increases in delta activity for 15 min, most dominant at the frontotemporal and occipital leads (max. +219% O1). Frontal and occipital beta 1 and beta 2 power (max. +131% and +124% at O1, respectively) was immediately increased after the bolus injection. No EEG changes occurred at central region Cz, and no interhemispheric EEG differences were noted. Theta, alpha 1, and alpha 2 power remained unchanged. CONCLUSION: The current data demonstrate simultaneous changes in psychomotoric status as well as delta and beta spectral power during lidocaine infusion. These data could be an indication that the pronounced frontotemporal and occipital EEG changes are the electroencephalographic expression of subjective sensations.

Adult↗
PubMed1996

Intraoperative EEG changes in relation to the surgical procedure during isoflurane-nitrous oxide anesthesia: hysterectomy versus mastectomy.

STUDY OBJECTIVES: To investigate topographical changes in electroencephalographic (EEG) frequencies and spectral power density in relation to different surgical procedures (abdominal hysterectomy versus mastectomy) during steady-state isoflurane-nitrous oxide (N2O) anesthesia. DESIGN: Prospective, nonrandomized, open study. SETTING: University hospital. PATIENTS: 34 ASA status I and II patients scheduled for elective abdominal hysterectomy or mastectomy. INTERVENTIONS: 12 patients were studied without surgery (Group I, control). 22 patients were studied for the first 14 minutes following skin incision during hysterectomy (Group 2, n = 11) or mastectomy (Group 3, n = 11). MEASUREMENTS AND MAIN RESULTS: Anesthesia was maintained with 0.6% isoflurane in 66% N2O in oxygen (O2). EEG was recorded via 17 channels followed by calculation of spectral power densities in selected frequency bands for each recording site. In addition, heart rate, mean arterial pressure (MAP), end-tidal carbon dioxide tensions, and isoflurane concentration were recorded. Total observation time was 20 minutes in all groups. At baseline, EEG variables were comparable in all groups. The EEG demonstrated slow wave activity superimposed with alpha waves. Start of surgery resulted in increases of slower waves and decreases in alpha activity. In both surgical groups, these EEG changes were most pronounced at frontal recording sites (p < 0.05) with differences in the frequency content. In Group 2 (hysterectomy), delta-activity became dominant, whereas in Group 3 (mastectomy), a shift to theta waves was observed. During surgery MAP was increased by 40% (Group 2; p < 0.05) and 21% (Group 3; p < 0.05), respectively. CONCLUSIONS: These results show that specific surgical procedures may induce EEG slow wave activity to a different degree. The EEG response varied in relation to the surgical procedure and/or the intensity of noxious stimulation. Mastectomy resulted in the appearance of theta activity whereas, during laparotomy, the EEG frequency content was shifted to delta waves. The topographical analysis indicates spatial inhomogeneities in the EEG responses with a dominance at frontal areas. From this findings, it may be concluded that the electrode montage used for intraoperative EEG recordings has to be carefully selected.

Adult↗
PubMed1996

[Neuromuscular and cardiovascular effect of mivacurium in anesthesia induction in patients with renal failure].

OBJECTIVE: Mivacurium produces a prolonged neuromuscular block (NMB) in anuric patients (13), in spite of its rapid hydrolysis by pseudocholinesterase (PChE) which is independent of renal function (17). In the present study the pharmacodynamics and the cardiovascular effects of a bolus dose of mivacurium (0.15 mg/kg) in relation to impairment of renal function were evaluated. METHODS: 60 patients (ASA class 2-4) were assigned to one of three groups according to the degree of renal dysfunction. Creatinine clearance (Krea-Cl) as a measure of renal function was calculated using weight, age, sex and serum creatinine concentrations. Group C (control): Krea-Cl > 50 ml/min; group P (preterminal): 20 ml/min < Krea-Cl < 50 ml/min; group T (terminal): Krea-Cl < 20 ml/min. PChE activity and dibucaine numbers were assessed preoperatively. Neuromuscular transmission (Train-of-Four) was monitored using electromyography (Relaxograph, Datex Inc.) with stimulation of the ulnar nerve. The response was recorded from the hypothenar muscle. Five minutes after induction of anaesthesia with propofol and fentanyl, 0.15 mg/kg mivacurium was given i.v. over 30 s. 150 s later patients were intubated. Anaesthesia was maintained by propofol (2-10 mg/kg/h) and fentanyl (0-5 micrograms/kg/h) infusion. Patients were ventilated with oxygen/nitrous oxide (FiO2 = 0.35). As soon as T1 recovered to 5% or more, mivacurium was administered continuously and this part of the study was finished. Times of onset (onset 10; onsetmax), maximal neuromuscular block (NMBmax), neuromuscular block when intubation was started (NMBTubus), and duration 5% (dur 5) were calculated. Arterial blood pressure and heart rate were recorded before anaesthesia, after induction of anaesthesia, 2-times after mivacurium application, and after intubation. All data were compared using Kruskal-Wallis test corrected for multiple comparisons, Friedman test, or chi 2-test (*: p < 0.05). Logarithms of dur 5 and PChEd were correlated using linear regression. RESULTS: Demographic data were comparable between all groups. PChEd was 3.7 (3.0/4.1) kU/l in group C, 3.2 (2.2/4.8) kU/l in group P, and 3.5 (2.5/4.0) kU/l in group T, respectively. There were no differences between groups, neither in the NMBmax, in NMBTubus, or in onset times. But dur 5 was significantly longer in patients with renal impairment, both preterminal and also end-stage (medians: 11 min in group K, 16 min in group P, 17 min in group T). Emphasis, however, is put on the broad range between 5 and 47 min of dur 5 in group P, and between 6 and 53 min in patients of group T which is clinically more important than the differences in the median values. Dur 5 correlates with PChEd (p = 0.0001). Intubation conditions were excellent (relaxed vocal cords, easy passage of the tube, without coughing) in approximately 70% of all 59 patients without significant differences between groups. In 8 patients conditions were poor (successful intubation, inspite of moderately adducted vocal cords, but moderate coughing after passage of the endotracheal tube). There were no clinically relevant hemodynamic changes in each group in the time between injection of 0.15 mg/kg mivacurium slowly and intubation 2.5 min later. DISCUSSION: Our findings suggest that 0.15 mg/kg mivacurium is an effective and safe intubation dose in healthy patients as well as in patients with renal impairment, inspite of a prolonged duration in patients with renal impairment. Low PChE in some, but not in all patients with a renal dysfunction indicates involvement of impaired hepatic function. There was a close correlation between the PChEd and dur 5. Therefore mivacurium dosage should be reduced in patients with compromised renal function, mainly if there are additional systemic, especially hepatic diseases. Thus, in patients with impaired renal function, relaxometry may be of high valu

Adolescent↗
PubMed1996

[Attempt at a definition of the individual anesthesia level by repetitive pain stimulation: correlation with EEG findings].

AIM: Previous studies using EEG for assessment of depth of anaesthesia correlate anaesthetic concentration with the anaesthetic stage. This procedure neglects the well known effect of individual different susceptibility to anaesthetics. Thus, patients receiving similar concentrations of anaesthetics may not necessarily be at the same level of "anaesthetic depth". The aim of this study was to define an interindividual comparable level of anaesthesia by recording the autonomic cardiovascular reaction to a standardised painful stimulus (tetanic stimulus, 80 mA, 100 Hz). METHODS: In 61 patients undergoing orthopaedic surgery general anaesthesia was performed with isoflurane in 66% N2O. Starting from 0.4% isoflurane, endtidal isoflurane concentration was increased in a stepwise manner (0.1% isoflurane) until the patient did not show any relevant cardiovascular reaction (increase of heart rate and/or blood pressure < 10%) after tetanic stimulation of the ulnar nerve. If patients demonstrated no haemodynamic changes at 0.4% isoflurane, the concentration was decreased until a relevant cardiovascular reaction was registered. During each steady state period multichannel EEG was recorded and mean values of power density (median: microV2/Hz) were computed. RESULTS: Comparing EEG-results between both groups exhibiting a cardiovascular reaction (CVR+ , median endtidal Iso: 0.5%) and without reaction (CVR- , median endtidal Iso: 0.6%) an increase in low frequency bands and a significant decrease in high frequencies was found (Wilcoxon-test, p < 0.05). In contrast, comparing EEG-data only in relation to endtidal isoflurane concentration neglecting individual haemodynamic responses, no differences of power density in high frequency bands were detected. CONCLUSION: This method to define individual depth of anaesthesia as described, results in more consistent EEG patterns and may be useful in relating EEG to depth of anaesthesia.

Adult↗
PubMed1996

Ketamine blocks currents through mammalian nicotinic acetylcholine receptor channels by interaction with both the open and the closed state.

Single channel recordings have shown that ketamine (Ket) decreases the open time of the nicotinic acetylcholine receptor channel (nAChR). The present experiments on simultaneous openings of the nAChRs of mouse myotubes investigate the interaction of Ket with the open as well as with the closed state of the channels. The patch-clamp technique was used to record currents activated by 10(-4) M acetylcholine (ACh) in the outside-out mode. ACh together with increasing concentrations of Ket was applied with a piezo-driven system. In a second protocol, the patches were preexposed to Ket before activation with ACh. With addition of Ket, the currents showed a biexponential decay, indicating an open-channel block. The peak current amplitude decreased reversibly and in a concentration-dependent manner. The rate constants of block (b+1) and of unblock (b-1) were modeled by computer simulation and were found to be: b+1 = 3 x 10(6) M/s, b-1 = 100/s. Preexposure of the patches to Ket revealed an additional block with a KD of approximately 2 x 10(-6) M, which is below clinical concentrations. These data suggest that Ket also interacts with the closed state of the nAChR.

Acetylcholine↗