Comparison of the amnesic effects of propofol and isoflurane anesthesia

Networks of interstitial cells of Cajal embedded in the musculature of the gastrointestinal tract are involved in the generation of electrical pacemaker activity for gastrointestinal motility. This pacemaker activity manifests itself as rhythmic slow waves in membrane potential, and controls the frequency and propagation characteristics of gut contractile activity. Mice that lack a functional Kit receptor fail to develop the network of interstitial cells of Cajal associated with Auerbach's plexus in the mouse small intestine and do not generate slow wave activity. These cells could provide an essential component of slow wave activity (for example, a biochemical trigger that would be transferred to smooth muscle cells), or provide an actual pacemaker current that could initiate slow waves. Here we provide direct evidence that a single cell, identified as an interstitial cell of Cajal by light microscopy, electron microscopy and expression of Kit mRNA, generates spontaneous contractions and a rhythmic inward current that is insensitive to L-type calcium channel blockers. Identification of the pacemaker of gut motility will aid in the elucidation of the pathophysiology of intestinal motor disorders, and provide a target cell for pharmacological treatment.     

Comparison of midazolam with propofol for sedation in outpatient bronchoscopy

Two children are described who had microphthalmia (one with unilateral and one with bilateral) noted at birth, and whose early onset of poor linear growth and weight gain led to a diagnosis of hypopituitarism prior to two years of age. Both children had growth hormone and thyroid-stimulating hormone deficiencies, and evidence of partial ACTH deficiency. Administration of growth hormone resulted not only in rapid linear growth but it also reversed the poor weight gain and head growth noted in these children. These cases suggest that hypopituitarism and microphthalmia may be associated with each other more frequently than has been recognized previously.     

Comparison of sedative and analgesic/anesthetic effects induced by medetomidine, acepromazine, azaperone, droperidol and midazolam in laboratory pigs

The sedative and analgesic/anesthetic effects of medetomidine, acepromazine, azaperone, droperidol and midazolam were compared in laboratory pigs. In these sedatives, medetomidine produced the most profound degree of sedation with greater drowsiness than was achieved by other sedatives tested. Medetomidine induced sedation accompanied with weak analgesia and muscle relaxation smoothly and quickly and depressed arousal reaction deeply as compared with other sedatives. Pigs given medetomidine were not aroused easily even by moderately rough stimulation for approximately 60 min after injection.     

The effects of midazolam or propofol followed by suxamethonium on the QT interval in humans

Atretic encephaloceles or myelomeningoceles are frequently solid due to hamartomatous proliferation of fibrous tissue and blood vessels. Because of the fibrous nature of the tumor with no cystic cavity and unusual location with no connection to CNS, they are frequently regarded as insignificant hamartomas. Apart from this terminology, they are also described as cutaneous meningiomas or hamartomas with ectopic meningothelial elements by the presence of meningothelial cells. We report a case of atretic encephalocele in the parietal scalp of an 8 year-old boy and a case of myelomeningocele in the posterior mediastinum of a 31 year-old woman. The terms atretic encephalocele and myelomeningocele are more appropriate for these cases because they include their pathogenesis and the non-neoplastic nature of the lesion.     

Anesthesia induction for laryngeal mask insertion--comparison of propofol with midazolam and propofol with thiopental

STUDY DESIGN: Radiographs and charts of 61 patients sustaining cervical spine trauma were studied prospectively to determine the incidence of vertebral artery injuries and possible correlative factors. Statistical analysis was conducted using chi-square testing of a two-way classification system. OBJECTIVES: To elucidate the incidence of vertebral artery injuries associated with cervical spine trauma, and to determine the value of various factors in predicting the existence of a vertebral artery injury. SUMMARY OF BACKGROUND DATA: During a 7-month period, 61 patients (41 male patients, 20 female; average age, 40.3 years) with cervical spine trauma were studied. METHODS: All patients admitted to the authors' hospital with cervical spine injuries underwent magnetic resonance imaging and magnetic resonance angiography of their cervical spine. All magnetic resonance angiographies were examined for vertebral artery injury. Data on demographics and the injury were recorded. RESULTS: Complete disruption of blood flow through the vertebral artery was demonstrated by magnetic resonance angiography in 12 of the 61 patients (19.7%). Ten of the 12 patients (83%) had either flexion distraction or flexion compression injuries. Age, sex, mechanism of injury, neurologic impairment, and associated injuries were not statistically significant in predicting the presence of a vertebral vessel occlusion. CONCLUSION: The findings in this study may support the need for vertebral vessel evaluation in selective patients, particularly those with flexion injuries and with neurologic symptoms consistent with vertebral artery insufficiency syndrome that do not correlate with the presenting bone and soft-tissue injuries.     

Overnight sedation with midazolam or propofol in the ICU: effects on sleep quality, anxiety and depression

OBJECTIVE: To assess and compare the impact of overnight sedation with midazolam or propofol on anxiety and depression levels, as well as sleep quality, in non-intubated patients in intensive care. DESIGN: Open, comparative prospective, randomised study. SETTING: Surgical intensive care unit (ICU) in a university hospital. PATIENTS: 40 conscious patients expected to stay in the ICU for at least 5 days who were admitted following trauma or elective orthopaedic, thoracic or abdominal surgery. MEASUREMENTS AND RESULTS: Evaluation of a self-assessment scale (Hospital Anxiety and Depression Scale, HAD) on the day following the 1st, 3rd and 5th night of sedation with either midazolam or propofol. Heart rate, pulse oximetry and blood gases were monitored. Eight patients were excluded from the analysis. The level of anxiety was severe (HAD > 10) in 31% of the patients receiving midazolam and in 26% (p = 0.1) receiving propofol after the first night of sedation with no significant improvement over the next few days. The levels of depression remained high (> 10) in 54% of patients receiving midazolam, and in 16% of the patients receiving propofol (p = 0.15). Sleep quality tended to improve during the study in the two groups. CONCLUSIONS: These data show that half of the patients in the ICU experienced high levels of anxiety and depression during the first 5 post-operative or post-trauma days in the ICU. The beneficial effects of sedation on sleep quality were comparable for midazolam and propofol, regardless of a lack of improvement in anxiety and depression. However, an improved quality of sleep could help to re-establish a physiological night and day rhythm.     

Ethanol and pentobarbital: Comparison of behavioral and subjective effects in sedative drug abusers.

The behavioral and subjective effects of acute oral doses of placebo, ethanol (0.5, 1.0, and 2.0 g/kg), and pentobarbital (150, 300, 600, and 750 mg/70 kg) were compared in 8 male volunteers with histories of sedative drug abuse using a double-blind, double-dummy, cross-over design. Ethanol and pentobarbital produced similar dose-related decrements in psychomotor and cognitive performance and exhibited a similar profile of effects on staff- and participant-rated measures. There was some evidence indicating that, at the highest dose, pentobarbital was perceived by participants as being more sedating than ethanol and that pentobarbital has a greater abuse liability than ethanol. In conjunction with the results of previous human laboratory studies comparing the effects of different types of sedative-hypnotic drugs, these results support a mostly barbituratelike rather than benzodiazepinelike profile of effects for ethanol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of etomidate, propofol, and midazolam on calcium and potassium channel currents in canine myocardial cells

BACKGROUND: Intravenous anesthetics etomidate, propofol, and midazolam produce negative inotropic effects of various degrees. The mechanism underlying these differences is largely unknown. METHODS: The effects of intravenous anesthetics on L-type Ca2+, transient outward and inward-rectifier K+ channel currents (ICa, IKto, and IK1) were compared in canine ventricular cells using the whole-cell voltage-clamp technique. ICa and IK were elicited by progressively depolarizing cells from -40 to +40 mV, and from -90 to +60 mV, respectively. The peak amplitude and time-dependent inactivation rate of ICa and IK were measured before, during, and after the administration of equimolar concentrations (5, 30, or 60 microM) of etomidate, propofol, or midazolam. RESULTS: Exposure to etomidate, propofol, and midazolam produced a concentration-dependent inhibition of ICa. Midazolam was the most potent intravenous anesthetic; at 60 microM, etomidate, propofol, and midazolam decreased peak ICa by 16 +/- 4% (mean +/- SEM), 33 +/- 5%, and 47 +/- 5%, respectively. Etomidate, propofol, and midazolam given in a 60-microM concentration decreased IKto by 8 +/- 3%, 9 +/- 2%, and 23 +/- 3%, respectively. IK1 was decreased by 60 microM etomidate and midazolam by 20 +/- 6% and 14% +/- 5%, respectively. Propofol had no effect on IK1. CONCLUSIONS: At equimolar concentrations, intravenous anesthetics decreased the peak ICa, IKto, and IK1 with various degrees of potency. Effects of anesthetics on ICa were significantly greater compared with their effects on K+ currents. These findings suggest that the negative inotropic actions of etomidate, propofol, and midazolam are related, at least in part, to decreased ICa. Some effects, such as IK inhibition, may partially antagonize effects of decreased ICa. Indeed, the final effect of these intravenous anesthetics on myocardium will be the sum of these and other sarcolemmal and intracellular effects.     

Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens

Small angle X-ray diffraction was used to examine arterial smooth muscle cell (SMC) plasma membranes isolated from control and cholesterol-fed (2%) atherosclerotic rabbits. A microsomal membrane enriched with plasma membrane obtained from animals fed cholesterol for up to 13 weeks showed a progressive elevation in the membrane unesterified (free) cholesterol:phospholipid (C/PL) mole ratio. Beyond 9 weeks of cholesterol feeding, X-ray diffraction patterns demonstrated a lateral immiscible cholesterol domain at 37 degrees C with a unit cell periodicity of 34 A coexisting within the liquid crystalline lipid bilayer. On warming, the immiscible cholesterol domain disappeared, and on cooling it reappeared, indicating that the immiscible cholesterol domain was fully reversible. These effects were reproduced in a model C/PL binary lipid system. In rabbits fed cholesterol for less than 9 weeks, lesser increases in membrane C/PL mole ratio were observed. X-ray diffraction analysis demonstrated an increase in membrane bilayer width that correlated with the C/PL mole ratio. This effect was also reproduced in a C/PL binary lipid system. Taken together, these findings demonstrate that in vivo, feeding of cholesterol causes cholesterol-phospholipid interactions in the membrane bilayer that alter bilayer structure and organization. This interaction results in an increase in bilayer width peaking at a saturating membrane cholesterol concentration, beyond which lateral phase separation occurs resulting in the formation of separate cholesterol bilayer domains. These alterations in structure and organization in SMC plasma membranes may have significance in phenotypic modulation or aortic SMC during early atherogenesis.     

Respiratory effects of intravenous midazolam

Thirty-four healthy, young-adult patients receiving intravenous midazolam for third-molar surgery had their respiratory parameters measured by respiratory inductive plethysmography. Tidal volume and minute volume showed significant changes during the initial 5-10 minutes of sedation, the changes being maximal during the first 5 minutes from the completion of injection of midazolam. The measurement of phase angle, an indicator of respiratory asynchrony, showed no significant change from normal, although a few patients showed some asynchrony of breathing, suggesting some amount of respiratory obstruction. A few patients showed a short period of apnoea and a small fall in the oxygen saturation. None of these changes caused any clinical concerns. It is suggested that the absence of stimulation after injection of midazolam, particularly in the initial few minutes, may contribute to the potential onset of respiratory problems.     

The effect of midazolam and propofol on interleukin-8 from human polymorphonuclear leukocytes

Anesthetics and sedatives contribute to postoperative immunosuppression. Interleukin-8 (IL-8) is a chemotactic and activating factor that mediates neutrophil adhesion and margination and is essential for host defense. We investigated the effect of anesthetics on isolated human polymorphonuclear leukocyte production of IL-8. Healthy human polymorphonuclear leukocytes were isolated using a single-step density gradient and stimulated with lipopolysaccharide in the presence of varying concentrations of propofol or midazolam for up to 20 h. IL-8 was measured in both culture supernatants and cell lysates using enzyme immunoassay, and IL-8 mRNA in cells was measured using Northern blotting and phosphorimaging. Data were analyzed using Kruskal-Wallis analysis of variance or the Mann-Whitney U-test as appropriate. Lipopolysaccharide increased extracellular accumulation of interleukin-8, which was suppressed by both propofol (P = 0.025) and midazolam (P = 0.028). However, intracellular IL-8 increased with exposure to lipopolysaccharide (P = 0.028) and remained increased with both anesthetics. Northern blot analysis also revealed increased IL-8 mRNA levels in the presence of both midazolam and propofol, which was confirmed by molecular imaging. These data strongly suggest that the anesthetics modulate transport or secretion of IL-8 protein from the cell. Suppression of IL-8 by anesthetics and sedatives may predispose postoperative and intensive care patients to infection. Implications: Anesthesia causes immune suppression and alters neutrophil function. We investigated the effect of propofol and midazolam on interleukin-8, a neutrophil chemotactic agent in human neutrophils. Both anesthetics decreased extracellular interleukin-8 accumulation, but intracellular levels and mRNA remained high. This suggests that propofol and midazolam alter interleukin-8 secretion from cells.     

The effect of propofol on midazolam metabolism in human liver microsome suspension

We have studied the inhibitory effects of propofol on the metabolism of midazolam using human liver microsomes. In addition, we also investigated whether the lipid in which propofol is solubilised inhibits the metabolism of midazolam. Only high concentrations of propofol (> 100 mmol), greater than those found in clinical practice, inhibited the metabolism of midazolam. The lipid had no effect on the metabolism of midazolam. This study differs from other laboratory studies looking at the inhibitory effects of propofol. These showed inhibition at concentrations similar to those seen in patients. The reasons for the differences may be explained by the use of different substrates or methodology. Propofol may be an enzyme inhibitor, but this remains to be shown to be important in patients.     

The effects of midazolam on oxygen consumption and the level of vigilance. The possibility of the sedative effect of the plexiglas dome (canopy) of the Deltatrac indirect calorimetry device

We investigated the effect of intravenous magnesium, a N-methyl-D-asparate (NMDA) receptor antagonist, in 8 patients suffering from neuropathic pain (post herpetic neuralgia or causalgia etc.). After the nerve block, magnesium sulphate (0.5 mol.l-1) 5 ml was administered intravenously by bolus infusion taking 5 min, followed by continuous infusion of the same dose for one hour. All patients were treated with this therapy once a week. In 4 patients, VAS score decreased 3 points or more when this therapy had been administered 3 to 11 times. In 2 patients, VAS score did not change, and the analgesic effect of magnesium was not certain in other 2 patients. Some patients felt heat sensation immediately after the bolus infusion of Mg, and had a good sleep after this therapy. However, there were not any severe side effects and significant change in HR or BP. We conclude that this therapy with magnesium once a week is safe and effective for relieving neuropathic pain.     

Punishment alters the discriminative stimulus effects of midazolam.

Experiment 1 examined the effects of punishment on the discriminative stimulus (DS) effects of midazolam (M) and pentobarbital (P) in 3 pigeons. Sessions began with a fixed-interval (Fl) 3-min schedule of food reinforcement. After 40 min, either saline (S) or 0.56 mg/kg of M was injected. A drug-discrimination (DD) component began 10 min later. Pecking the left key produced grain after S injections, whereas pecking the right key produced grain after M. Dose-response curves for M and P were obtained under these conditions and also when every 30th peck during the Fl was punished by shock. The introduction of punishment increased sensitivity to the DS effects of M and P. Experiment 2 examined whether a punishment history increases sensitivity to the DS effects of M. After DD training and testing, pecking was punished for 10 sessions. This history shifted the M dose-response curve to the left for 3 of 4 pigeons. These results emphasize the contribution of behavioral variables to the DS effects of drugs. Environmental variables appear to play a prominent role in guiding sensitivity to the subjective effects of drugs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A comparative study of midazolam to meperidine/promethazine as an IM sedative technique for the pediatric dental patient

This study evaluated the efficacy and safety of midazolam (0.2 mg/kg) as an IM sedative agent in the pediatric population as compared to the standard IM meperidine (2.0 mg/kg)/promethazine (1.0 mg/kg) sedation technique. Ten pediatric dental patients, ASA Class I, were evaluated in this double-blind, randomized, crossover study. The patients ranged in age from two to four years. Vital signs, sedation levels, and anxiety levels were evaluated. Midazolam was shown to be safe, but the inferior drug compared to the standard IM meperidine/promethazine sedation technique.     

The dose-dependent effects of oral premedication with midazolam

OBJECTIVE: The aim of this study was to examine the psychological effects, well-being and side effects after various doses of oral midazolam medication. METHODS: After informed consent has been obtained and following the approval by the institutional ethical committee, 80 adult patients in the ASA physical status I and II were randomly assigned to one of five different premedication groups: 3.75, 7.5, 11.25, 15 mg midazolam, and placebo. The medication was given in a double-blind fashion 60 min before induction of general anaesthesia for various surgical procedures. At 3 definite stages (before premedication, 30 and 60 min after premedication), blood pressure, heart rate, transcutaneous oxygen saturation and respiratory rate were measured. Sedation and well-being were graded according to a 5-point scale, and the subjective anxiety level was assessed according a visual analogue scale (range 0-100 mm). Anterograde and retrograde amnesia were measured by recall of auditive and visual stimuli. Finally, patients were asked whether in case of future surgery they would prefer the same or a different medication. RESULTS: Demographic data were similar in all groups. There was no significant difference in respiratory rate, oxygen saturation, blood pressure or heart rate. Alertness declined only after 60 min in the groups treated with 7.5 mg and more midazolam. During the entire measurement period, anxiolysis was not different from placebo in any of the midazolam groups. In comparison to placebo, all midazolam groups showed a statistically significant and dose dependent anterograde amnesia for visual stimuli. Subjective well-being scores showed no differences between the groups. Only few side effects were seen following doses of 7.5 mg and higher, including ptosis, strabismus, diplopia, speech disorders, disorientation and vertigo. The majority of patients in all groups indicated a wish for the same medication in case of future anaesthesia for surgical interventions. CONCLUSIONS: Midazolam administered orally prior to surgical procedures showed marked interindividual variability. Sedation and amnesia were dose-dependent and were evaluated by the patients as acceptable. Anxiolysis was not significantly different from placebo. A dose of 7.5 mg midazolam showed the best relation between desirable and undesirable effects. Adequate attention given to the patient by the anaesthesiologist prior to surgery seems to be as important and beneficial as oral medication with midazolam.     

Effects of midazolam and propofol on dopamine release from rat striatal slice using a fast-cyclic voltammetry system

In order to evaluate the difference in pharmacological mechanism between midazolam and propofol, we focused on the interaction between dopaminergic and GABAergic neurons in the striatum because of its important role in the regulation of motor system and arousal response, and examined these inhibitory effects on dopamine (DA) release induced by high-K from the rat striatal slice using the fast-cyclic voltammetry method. Between 0.1 and 200 nmol, the standard curve of DA was linear. The peak and the sensitivity of DA oxidation were different from those of norepinephrine and DA main metabolites. The dosages between 0.1 and 10 micro M of propofol significantly blocked the high-K evoked DA release, although the dosage of larger than 50 micro M of propofol potentiated DA release. In case of midazolam, the dosages between 0.1 and 50 micro M markedly suppressed DA release induced by high-K in a dose-dependent manner. The recovery time of DA release after removal of midazolam from incubation medium was longer than that seen in the treatment of propofol. In conclusion, propofol and midazolam inhibited high-K evoked DA release from striatal slice, although these efficacies were dissimilar. Furthermore the pharmacological effects of larger dosage of propofol was different from those obtained by its smaller dosages. These results suggest that the anesthetic actions of propofol and midazolam are partially related to inhibition of DA neuron A1 activity and that the excitatory symptom induced by a larger dose of propofol may be related to its potantiation of DA release.     

Cardiorespiratory effects of combined midazolam and butorphanol in isoflurane-anesthetized cats

A case is reported of a child born with a developmental field defect of the first branchial arch in whom there was partial obstruction of the oropharynx by a horseshoe-shaped mass of what was thought to be tonsillar tissue. 'Tonsillectomy' was performed but histopathological examination of the excised specimens showed them to be almost entirely made up of salivary gland tissue.     

Associative control of tolerance to the sedative effects of a short-acting benzodiazepine.

The role of Pavlovian conditioning in tolerance to the depressant effect of a benzodiazepine (midazolam) on the ambulatory activity of rats was examined. The depression of activity by low doses (1.0 and 4.0 mg/kg, ip) of midazolam diminished quickly over repeated doses given at 48-hr intervals (Experiment 1). Equivalent tolerance was observed in groups measured at 2 min and 30 min after drug injection. When challenged with saline, however, drug-tolerant animals tested immediately after injection were hyperactive in comparison with nontolerant controls, whereas equivalent groups tested 30 min after injection were not. A second context was designed, and its discriminability from the original was established by assessing context-specific suppression of activity following exposure to mild electric shock (Experiment 2). In Experiment 3A, although tolerant animals tested in the drug-associated context remained fully tolerant, a second group demonstrated a complete loss of tolerance when given the drug in a saline-associated context. Both groups were fully tolerant when tested again in the drug-associated context after 14 drug-free days. In Experiment 3B, tolerance was significantly reduced by 14 extinction exposures to the drug-associated environment without the drug. These results are uniquely predicted by associative models of drug tolerance and may have implications for the clinical use of this class of drugs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)