Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600097 (Sedation)
 1,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intramuscular neutrolysis with phenol has been used for 10 years in the management of spasticity in children. Best results depend on fastidious technique and realistic use of the procedure. Sedation or anesthesia was used in all cases -- 5% phenol in water was used for all procedures. The main indications were spasticity which interfered with function, either actual or potential, or with care. Where uninhibited vestibular or tonic neck reflexes affect muscle tone, or there is dystonia or athetosis, the procedure is less effective than where spasticity alone is present. Duration of relief of spasticity ranged from 1 month to more than 2 years. About one half of the lower extremity muscle treated required tenotomy later. Generally training was required after the procedure to obtain improved function. A representative sample of muscles treated, repeat procedures, and later surgery is discussed. The procedure is recommended for use in the management of spasticity in children as a way of improving function and/or care.
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PMID:Intramuscular neurolysis for spasticity in children. 47 67

The pharmacokinetics of midazolam, a water soluble 1,4-benzodiazepine, has been studied in 12 patients (11 male, 1 female; age range 19-57 years) with epilepsy. All patients were taking hepatic enzyme inducing antiepileptic drugs (AEDs) on a regular basis. Midazolam (5 mg) was administered intravenously and 1 week later midazolam was administered intramuscularly, the dose used being dependent on the sedative response to the intravenous dose (10 mg, n = 2; 7 mg, n = 8; 5 mg, n = 2). Serial blood samples were collected at timed intervals for 5-7 h. After intravenous administration initial distribution was rapid with a mean half-life (t 1/2 alpha) of 0.06 +/- 0.03 h followed by a terminal half-life (t 1/2 beta or gamma) of 1.5 +/- 0.3 h. Volume of distribution was 0.62 +/- 0.27 l/kg. After intramuscular administration midazolam was rapidly absorbed with peak serum concentrations achieved at 25 +/- 23 min. Two patients showed delayed absorption. Mean terminal half-life was 2.8 +/- 1.7 h. The absolute bioavailability of intramuscular midazolam was calculated in 11 patients as 87 +/- 18%. Sedation was rapid (less than 1-2 min) but transient (7-75 min) after intravenous and slower (2-30 min) and for a longer period (20-120 min) after intramuscular administration. Since intravenous administration of AEDs including diazepam is not always feasible in status epilepticus there are obvious advantages in having an effective intramuscular formulation. Our data suggest that midazolam may be such a drug.
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PMID:A comparative pharmacokinetic study of intravenous and intramuscular midazolam in patients with epilepsy. 181 58

Multiple bone marrow aspirations or biopsies and lumbar punctures are a necessary part of the diagnosis and treatment of many pediatric cancer patients. Pharmacologic sedation may decrease the distress associated with these procedures. Midazolam (MDZ, Versed) is a water-soluble, rapid-onset, short-duration benzodiazepine that has not been studied widely in children. We prospectively evaluated safety and recovery parameters for intravenous MDZ used for conscious sedation by oncologists (without an anesthesiologist in attendance) for 70 procedures (bone marrow aspirations, lumbar punctures, or bone marrow aspirations plus lumbar punctures) in 24 ambulatory pediatric cancer patients, aged 1.5 to 15.5 years. MDZ was used alone or in combination with morphine or fentanyl. Respiratory rate, oxygen saturation, blood pressure, and heart rate were monitored. Sedation, anxiolysis, and recovery were assessed with a behavior score and a modified recovery room discharge score. Restraint was not required in 45% of the procedures. In no case was a respiratory rate less than 12 observed. In nine procedures (13%), an oxygen saturation less than or equal to 90 occurred, all within 10 minutes after the last dose of MDZ. Ten procedures (14%) required verbal stimulation to take deeper breaths. Two patients did not respond immediately to verbal stimulation and received face-mask oxygen. Hypoxemia was not correlated with opioid use. Hypoxemia appears to be related to total MDZ dose and may occur with normal respiratory rates; all cases resolved with verbal stimulation or face-mask oxygen without specific airway maneuvers or assisted ventilation. Heart rate and blood pressure remained stable in all 70 procedures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Midazolam for conscious sedation during pediatric oncology procedures: safety and recovery parameters. 195 34

The purpose of this study was to determine the effect of oral estazolam at two and three times the usually recommended dosage (2 mg) on ventilation and respiratory drive during wakefulness. Sixty healthy subjects were randomized to receive a single oral dose of either: 1) estazolam 4 mg; 2) estazolam 6 mg; 3) placebo; or 4) morphine 0.15 mg/kg. Predrug and postdrug measurements were obtained for ventilation, respiratory cycle timing, metabolic rate, temperature, and ventilatory and mouth occlusion pressure (P0.1) responses to exogenous CO2. No difference between placebo and the study drugs was noted during eupneic breathing. During administration of exogenous CO2, morphine caused a decrease in the slope of the ventilatory (-0.4 +/- 0.1 L/min/mm Hg, P = .008) and P0.1 (-0.22 +/- 0.06 cm H2O/mm Hg, P = .015) responses. Estazolam (4 and 6 mg) had no effect on the ventilatory response to exogenous CO2. However, estazolam (6 mg) caused the P0.1 at a PCO2 of 57 mm Hg to decrease (-0.67 +/- 0.30 cm H2O, P = .005). The preservation of ventilation with the highest dose of estazolam, despite the decrease in P0.1, indicates that a compensatory strategy independent of respiratory center drive may have been activated. Sedation was a common side effect of estazolam reported in 13% and 53% of subjects at the 4 mg and 6 mg doses, respectively. We conclude that a single, high dose of estazolam does not cause ventilatory depression during wakefulness in healthy subjects.
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PMID:Ventilatory response to single, high dose estazolam in healthy humans. 197 81

Ultrasonic imaging of infants and children using an automated transducer water-path delay scanning system (Octoson) overcomes many of the technical difficulties of contact B mode ultrasound imaging and computed tomography. These disadvantages relate to small patient size, motion artifacts, hypothermia, and lack of patient cooperation. Sedation may be required for either conventional study. The automated water-path system is soothing to small children, maintains the body temperature of infants, and avoids direct transducer contact. Sedation is not necessary. Excellent resolution, shorter scan time than computed tomography, and greater flexibility of patient and transducer positioning allows much more complete imaging information. In addition, the panoramic view obtained using this modality serves to demonstrate the complete lesion and its relationship to surrounding structures.
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PMID:Octoson imaging in pediatric urology. 330 94

The sedative effects of a relatively lipid-soluble and a water-soluble beta-blocker were compared in 20 male hypertensives, 30 to 60 years old. In a blinded, randomized, crossover study, critical flash fusion frequency and computerized Stroop Word Test were used to assess psychomotor function parameters during a drug-free control day and then following 14 days of either metoprolol, 150 mg daily, or atenolol, 100 mg daily, treatment. Both drugs caused subtle but significant reductions in both parameters of sedation (critical flash fusion frequency and computerized Stroop Word Testing). Sedation was significantly related to serum concentrations of both drugs. The maximum drug-induced change was 17.2% +/- 9% for metoprolol and 19.6% +/- 3% for atenolol. The duration of effect was six hours after atenolol and two hours after metoprolol. Blood pressure control for all patients was similar during both treatment phases. These results demonstrate that relative lipid solubility does not reliably predict the neurologic effects of beta-blockers. The intensity of drug-induced sedation was similar, but the water-soluble agent produced a longer duration of sedative activity.
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PMID:Lipid-soluble and water-soluble beta-blockers. Comparison of the central nervous system depressant effect. 354 24

The present experiment sought to determine in rats if 1) tolerance develops to the amnesic effect of diazepam after chronic treatment, 2) the sedative and amnesic effects of diazepam can be dissociated via differential rates of tolerance development, and 3) withdrawal from long-term diazepam treatment affects mnemonic processes. Rats were given diazepam (3 mg/kg) acutely or chronically for 5, 15, or 30 d prior to behavioral testing. Sedation was assessed as exploratory activity in an open field and amnesia was assessed as spatial learning in the Morris water maze. Tolerance to the sedative effect of diazepam was exhibited after 5 d pretreatment whereas tolerance to the amnesic effect of diazepam was exhibited only after 30 d pretreatment. Withdrawal from diazepam produced a transitory and mild disruption of spatial learning. The data demonstrate 1) tolerance can develop to the amnesic effect of diazepam with extended treatment, 2) the sedative and amnesic effects of diazepam are largely independent, and 3) withdrawal from chronic diazepam treatment can retard optimal learning.
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PMID:Tolerance develops to the spatial learning deficit produced by diazepam in rats. 907 73

The aim of this study was to assess oral premedication with midazolam in paediatric anaesthesia. Sedation, quality of induction, recovery time, acceptance and effects on gastric contents were analysed. This prospective, double blind, at random and controlled study was performed in 107 children, aged between three and ten years. They were divided into: group 1 (control, n = 29), group 2 (placebo) receiving 5 ml of water in the preoperative stage (n = 40), and group 3 (midazolam) with 0.75 mg.kg-1 midazolam by mouth (n = 38). Two children refused to take medication. In children aged five years or more (n = 48) of groups 2 and 3, acceptance of premedication was evaluated. The midazolam group showed a better level of sedation as compared with the placebo (P < 0.05). The recovery time was similar for the two groups. There were no statistically significant differences in gastric pH or residual volume among the three groups. It is concluded that midazolam given by mouth is an efficient and safe drug for premedication in paediatric anaesthesia.
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PMID:Oral premedication with midazolam in paediatric anaesthesia. Effects on sedation and gastric contents. 918 63

During cerebral ischaemia, glutamate is released in supraphysiological amounts and is toxic to brain tissue. This excitotoxicity is mediated by several glutamate receptor subtypes, including the ionotropic N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. Clinical trials of drugs that block the NMDA receptor in acute ischaemic stroke have been disappointing. No improvement in clinical outcome of stroke has been seen with competitive NMDA antagonists (selfotel) and non-competitive NMDA antagonists (dextrorphan, GV150526, aptiganel and eliprodil). The AMPA receptor differs in important ways from the NMDA receptor. It is the principal mediator of fast excitatory neurotransmission. This ligand-gated cation channel is primarily permeable to sodium rather than calcium. It is found in grey and white matter. It is expressed by oligodendrocytes. This distribution may provide neuroprotection for both grey and white matter. In a variety of animal models, reduction in infarct volume with AMPA blockade has been demonstrated. AMPA antagonists also show benefit in spinal cord ischaemia and trauma. The clinical development of safe and effective AMPA blockers has been hampered by poor water solubility and associated renal toxicity. A novel, highly water-soluble, competitive AMPA receptor antagonist, YM872 ([2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydroquinoxalin-1-yl]acetic acid monohydrate; Yamanouchi), has been identified. Phase I clinical trial data indicate that this agent can be safely administered in young and elderly subjects. Sedation and other CNS associated adverse events determine the ceiling dose and become more problematic with infusion times exceeding 24 h. Phase II studies of YM872 in acute ischaemic stroke are ongoing.
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PMID:Glutamate AMPA receptor antagonist treatment for ischaemic stroke. 1236 32

The main criteria for assessing conscious sedation (perhaps now more correctly termed "moderate sedation/analgesia") continue to be patient satisfaction and comfort, short duration, amnesia, and above all, patient safety. The problems reviewed last year - including the increasing pressure on endoscopy units to perform yet more procedures, reduce costs, and achieve shorter patient turn-around times - certainly have not gone away. Studies reviewed this year suggest that although many endoscopic procedures, such as oesophagogastroduodenoscopy (OGD), colonoscopy, and endoscopic ultrasonography (EUS) can indeed be performed without intravenous sedation, many patients still prefer to be sedated. Further papers on the possible role of ultrathin endoscopes in unsedated OGD are reviewed here. A study in Italy comparing virtual computed-tomographic (CT) colonography and conventional colonoscopy suggests that unsedated colonoscopy is unlikely to meet with wide acceptance. Audits of colonoscopy in both the United States and the United Kingdom suggest that there is still a long way to go before caecal intubation rates of more than 90 % are regularly attained. The evidence suggests that some endoscopists are using larger doses of a midazolam and pethidine combination than are generally recommended (particularly in elderly patients), and sedation-related deaths are still occurring. Impressively large clinical studies, particularly those from Switzerland, on the use of propofol administered by nonanaesthetists are leading to reconsideration of the earlier view that propofol should only be used by anaesthetists. If propofol is to be used more widely and become an agent administered by endoscopists (or nursing staff), then considerable improvements in the standard of airways management will be needed. Several new studies relating to bowel-cleansing agents and the use of a carbohydrate/electrolyte "cholera mixture" to prevent the associated intravascular volume contraction have been published. Warm water is a cheap and effective way of reducing colonic spasm during colonoscopy, and intraluminal peppermint oil is a good antispasmodic in the stomach as well as the colon. Sedation should still be regarded as one part of an overall "endoscopy package". Finally, more attention needs to be given to patients' complaints regarding what are often considered by endoscopists to be "trivial complications" if the patients are to have a positive experience of their examination that will lead to them being prepared to come back a second time.
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PMID:Preparation, premedication, and surveillance. 1472 52


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