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Biomedical subjects

R Dirksen

Publications and source records attributed to R Dirksen.

At least 55 records · Page 3Linked to original sources
PubMed1991

A system model for closed-circuit inhalation anesthesia. II. Clinical validation.

Recently, we described a basic model and its more elaborate variants to predict the uptake and distribution of inhalational anesthetics during closed-circuit anesthesia. As an initial clinical validation of the linear, continuous, 14-compartment basic model, the current study examined its predictive performance in 50 patients by comparing quantitatively the predicted and the measured alveolar concentration-time profiles after bolus injections of liquid isoflurane into the closed system during mechanical ventilation. The two versions of the model studied differed in the size of their peripheral shunt, as 0% (version A) and 16% (version B) of the cardiac output. A total of 15,744 alveolar concentrations of isoflurane (one per 10s period) were measured by mass spectrometry. For each measured concentration we used computer simulations of version A and version B to calculate a predicted concentration for both versions. For each patient we calculated the bias (indicating over- or underprediction) and the scatter of the prediction errors (indicating the typical error size). The bias and the scatter of the prediction errors, both given as mean (and standard deviation), were 2.25 (13.59) and 12.51 (5.84)% for version A and 12.00 (14.97) and 14.12 (6.54)% for B. Version A performed better than B: both the bias (P = 0.008) and the scatter (P less than 0.0001) were closer to zero for A. Logistic regression analysis showed for version A that scatter, but not bias, increased with age (P = 0.002). Gender, body mass index (weight x height-2), and number of injections per hour did not influence scatter or bias.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A system model for closed-circuit inhalation anesthesia. I. Computer study.

Developing a custom computer program to simulate the uptake, distribution, and elimination of inhalational anesthetics allows the anesthesiologist to address specific problems, but extensive skills are required to translate the involved processes first into a set of mathematical equations and then into a satisfactory computer program. The first step is often facilitated by solutions offered in the literature. The second step demands computer proficiency that is often not available, but this problem can be obviated by means of a special-purpose simulation language (SPSL). We therefore constructed a model for closed-circuit inhalation anesthesia with the aid of the block-structured SPSL TUTSIM. Noticeable differences with previous models are that the linear, 14-compartment basic model does not assume a constant alveolar concentration and mimics circulation times through the use of blood pools. Advanced features of the SPSL were used to develop variants of the basic model to simulate feedback-controlled isoflurane administration, nitrous oxide uptake, and the impact of a nonlinearity by incorporating the effect of enflurane on cardiac output. Two variants were concatenated to form a multiple model showing the concentration and second-gas effects. The model was capable of reproducing the anesthetic uptake from previous experimental studies for nitrous oxide. After its validation for other anesthetic agents, the model can be used for clinical, teaching, and research purposes. The SPSL freed the authors from the problems associated with computer programming and allowed them to concentrate on the structure of the model.

Anesthesia, Closed-Circuit↗
PubMed1991

Facilitation of spike-wave activity by the hypnotic etomidate in a rat model for absence epilepsy.

The epileptogenic effect of the short-acting hypnotic agent etomidate was investigated in WAG/Rij rats. Animals of this inbred strain show spontaneous spike-wave discharges and are regarded as a model for absence epilepsy. A dose-dependent increase in the total amount of spike-wave activity was found, when etomidate was injected intraperitoneally in doses of 1, 2.5, 5 and 10 mg/kg. At a dose of 10 mg/kg, spike-wave activity appeared almost uninterruptedly. Beginning with a dose of 5 mg/kg, the morphology of the spike-wave complexes changed after the administration of the drug; spike frequency decreased dose dependently from about 8 till about 4 Hz at 10 mg/kg. During spike-wave activity, animals were motionless and, certainly at 10 mg/kg of etomidate, were unresponsive to stimuli. For surgical anesthesia, a still higher dose of etomidate is necessary (20 mg/kg). It is concluded that etomidate facilitates the generation of spike-wave activity in rats with spontaneous absence seizures, presumably through its GABA-mimetic action.

Action Potentials↗
PubMed1990

Opioid receptors and pain.

A receptor site is considered to be a transducing factor for effect of the natural ligand. Endorphins and the drugs that mimic their effects (the opiates) are important for analgesia, and consequently the receptor sites involved in actions of opioid drugs are to be considered as relevant to the transmission of pain. The present review describes the distribution of the opioid receptor sites in the central nervous system, and links their presence to pain-specific areas of the central nervous system.

Analgesics↗
PubMed1990

Intrathecal somatostatin produces effects dependent on the interval between catheter implantation and drug injection.

Intrathecal (i.t.) injection of somatostatin has been reported to depress nociceptive reflexes as well as to cause severe disturbance of somatomotor performance. The present study was designed to assess the dependence of these effects on the dose and the interval between implantation of the catheter and i.t. injection of somatostatin in rats. The effects produced by i.t. injection of somatostatin consisted of an increase in the response latencies of nociceptive responses to noxious heat, impairment of motor performance and grooming behavior, convulsions, and death. Except for grooming behavior, these were related in incidence and degree to the dose and the interval, the potency of somatostatin being highest at short intervals. Sham operations also affected the effectiveness of somatostatin.

Animals↗
PubMed1988

Dipropylacetate-induced shaking behaviour in the rat: a role of spinal alpha 2-adrenoceptors.

The role of spinal adrenoceptors in di-n-propylacetate (DPA)-induced shaking behaviour was studied. The alpha 2-agonist p-aminoclonidine in a dose of 5 micrograms was found to suppress the DPA-induced body shakes when injected intrathecally but not when given intraventricularly. There was an enhancement of DPA-induced body shakes after the intrathecal injection of idazoxan while only a slight decrease was found after the intrathecal injection of prazosin. Intrathecal injection of idazoxan but not of prazosin proved to be effective to reverse the DPA-induced body shakes suppressed by p-aminoclonidine. Although the difference in effectiveness after intrathecal and intravenous injection was less than has been described for opiates there are several arguments that indicate an effect confined to the spinal cord. The present results further evidence the notion that the DPA-induced shaking behaviour shares common mechanisms with some of the morphine abstinence symptoms. The data indicate that spinal alpha 2-adrenoceptors are at least partly involved in the suppressive effect of p-aminoclonidine on DPA-induced shaking behaviour.

Adrenergic alpha-Agonists↗
PubMed1988

Automated charting of physiological variables in anesthesia: a quantitative comparison of automated versus handwritten anesthesia records.

Eight physiological variables--tidal volume, breathing rate, end-tidal carbon dioxide fraction, oxygen fraction in the anesthetic circuit, oxygen saturation by pulse oximetry, systolic and diastolic blood pressure, and heart rate--recorded on-line by a commercially available automated system were compared with the same variables recorded on handwritten anesthesia records. We quantified the differences between the automated and handwritten records generated from the same 30 patients (2,412 minutes of general anesthesia for elective eye surgical procedures). Considering the design of the study, we claim that the differences between both records were caused by the incompleteness or inaccuracy of the handwritten records, except in two instances. The amounts of missing or erroneous data for these eight physiological variables were expressed as fraction ("error fractions") of the time being recorded, designated EFm and EFe, respectively. For the first five variables the EFm on the handwritten records ranged between 0.23 and 0.31, and the EFe ranged between 0.01 and 0.06. For the last three variables the EFm range was 0.08 to 0.13, and the EFe range was 0.05 to 0.11. Most of these missing or erroneous data occurred during the period of induction (first 15 minutes) and at the end of the case (last 10 minutes). The EFm and EFe during induction had increased to 0.62 and 0.26, respectively, and to 0.76 and 0.06, respectively, at the end of the case. Erroneous data were observed on the automated records for the tidal volume during induction (EFe = 0.0044) and for the oxygen fraction during maintenance (EFe = 0.0024). The effect of averaging by the recordkeeper is discussed. The results of this study indicate the clinical relevance of automated record keeping.

Anesthesia↗
PubMed1987

The clinical use of the Ohmeda Automated Anesthesia Record Keeper integrated in the Modulus II Anesthesia System. A preliminary report.

While performing his complex array of tasks, the anesthesiologist is also responsible for maintaining an anesthetic record. Up to now, this has been done by hand. The clinical use of automated anesthesia record keeping is presently evaluated. The anesthesia records generated by the Ohmeda Automated Anesthesia Record Keeper integrated in the Modulus II Anesthesia System is compared to hand written records. The differences between the two records of identical patients are quantified as erroneous or missing data. With the criteria adapted, we found significant and clinically relevant differences which stress the importance of automated record keeping.

Anesthesiology↗
PubMed1986

Effects of the affinity ligands 14-beta-chloroacetylnaltrexone and 14-beta-bromoacetamidomorphine on [3H]-dihydromorphine binding sites in rat brain.

The aim of the present study was to examine the inhibitory effects in vitro of the affinity ligands 14-beta-chloroacetylnaltrexone (CAN) and 14-beta-bromoacetamidomorphine (BAM) to characterize the pharmacological specificity of the ligands for high and low affinity opioid binding sites. Rat brain membranes were incubated with 2.0 microM BAM or CAN, or their parent compounds (morphine and naltrexone, respectively) at 37 degrees for 45 min, and the membranes were washed extensively to remove the unbound ligand. The specific binding of 0.3 nM [3H]dihydromorphine ([3H]DHM) was reduced 32 +/- 7% in membranes treated with CAN and BAM, whereas specific binding in preparations treated with morphine and naltrexone was not significantly different from controls. An increased affinity of BAM and CAN relative to morphine and naltrexone could not account for the observed irreversible inhibition, since the relative affinity of CAN was similar to that of naltrexone and that of BAM was 10-fold less active than morphine. Saturation binding assays revealed that the affinity ligands selectively abolished a high affinity binding site (Kd = 0.3 nM, Bmax 95 fmoles/mg protein), which comprised approximately one-third of the total number of sites. The affinity of the remaining site (Kd = 4.0 nM) was not altered significantly. The results indicate that the inhibition caused by the affinity ligands is irreversible and represents inactivation of high affinity opioid binding sites in a relatively selective manner.

Animals↗
PubMed1985

Antinociceptive effects of intrathecally injected cholinomimetic drugs in the rat and cat.

Rats chronically implanted with intrathecal catheters displayed a dose-dependent increase in the hot-plate, tail-flick response latencies, and decreased the magnitude of the writhing response following the injection of certain cholinomimetics into the subarachnoid space through the indwelling catheter. The structure-activity relationship for these agents is oxotremorine greater than carbachol greater than acetylcholine + physostigmine much much greater than acetylcholine = nicotine-HCl = 0. Atropine, but not naloxone, strychnine, picrotoxin, curare or methysergide and phentolamine, reversed the antinociceptive effect. This suggests the involvement of muscarinic cholinergic mechanisms. Experiments with intrathecal injection of carbachol into the spinal subarachnoid space of cats fitted with intrathecal catheters also revealed a potent antinociceptive effect which was completely antagonized by atropine. The effect was somatotopically limited with the skin surfaces innervated by cord segments nearest the catheter tip showing the most significant effect with the shortest latency of onset. This observation, together with the absence of changes in general reflex motor function or postural control further indicated a selective spinal effectiveness of muscarinic agonists after low dose intrathecal administration.

Analgesics↗
PubMed1983

The relevance of cholinergic transmission at the spinal level to opiate effectiveness.

Rats chronically implanted with intrathecal catheters displayed a dose-dependent increase in the hot-place and tail-flick response latencies following the injection of morphine or nicomorphine into the subarachnoid space through the indwelling catheter. Naloxone inhibited the antinociceptive effect of both opiate drugs, but the inhibition of nicomorphine-induced antinociception was incomplete. To evaluate the importance of cholinergic mechanisms in opiate effectiveness, the interactions with atropine or physostigmine were evaluated. Atropine reduced the effects of morphine and abolished the effects of nicomorphine at the doses used. Physostigmine markedly potentiated morphine effectiveness, but had a negligible effect on nicomorphine effectiveness. It is proposed that these differences relate to a specific cholinergic mechanism involved in antinociception after intrathecal nicomorphine. The data indicate that at a spinal level cholinergic mechanisms are relevant to opiate effectiveness.

Analgesia↗
PubMed1980

Epidural opiate and perioperative analgesia.

Epidural injections of 5 mg nicomorphine in 20 ml 5% glucose wee given to 10 gynaecological patients to provide intra-operative and post-operative analgesia. Signs of changed nociception appeared within 5 min. The maximum change occurred within 20 min. Effectiveness was at least 3 1/2 h. After an observation period of 30 min, light general anaesthesia is supplemented to give excellent operating conditions. It is suggested that opiates produce these effects by a direct action on the endorphin "pain" modulatory system of human beings at spinal level.

Adult↗