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)

Primary hypoventilation (Ondine's curse), due to diminished sensitivity ofthe respiratory center to CO2, is very rare. Up to now only a few patients have been observed, ten of whom were children. Familial occurrence was reported in 1976 for the first time. The cases are described of a 10-year-old girl and her mother who both showed the typical clinical and pathophysiological symptoms. Our own observation also suggests that this unknown defect of respiratory regulation could be inherited. Sedation, anesthesia, or severe respiratory tract infection are life-threatening situations in these patients. Pulmonary hypertension and right heart failure are possible long-term complications.
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PMID:[Familial primary chronic type ventilation]. 86 15

Ondansetron is a selective 5-hydroxytryptamine type 3 receptor antagonist effective as an antiemetic in patients experiencing post-operative or cancer chemotherapy-induced nausea and vomiting. Currently, no information is available regarding the interaction of ondansetron with opioids, although a serotonin antagonist might be expected to modify some opioid actions. This study was designed to measure the effects of ondansetron on alfentanil-induced ventilatory depression and sedation in healthy male volunteers. Ventilatory drive (measured as the end-tidal CO2 necessary to produce a minute ventilation of 15 l/min) was determined in 29 subjects using a modification of the Read rebreathing technique. Sedation was measured by asking the subjects to complete visual analog scales. Alfentanil was administered as a bolus (5 micrograms/kg) followed by a continuous infusion (0.25-0.75 micrograms.kg-1.min-1) for at least 90 min. Study medication (ondansetron 8 or 16 mg or vehicle placebo) was then administered in a randomized, double-blind manner, and the alfentanil was infused for an additional 15 min. Measurements of ventilatory drive and sedation were made at baseline, during alfentanil infusion, after study medication, and at 30-min intervals after alfentanil was discontinued. Alfentanil produced significant ventilatory depression (P less than 0.001) and sedation (P less than 0.001) in all three groups. Neither placebo nor ondansetron produced further change in the intensity of either alfentanil effect. After discontinuation of the opioid, both ventilatory depression and sedation decreased, and the rate of recovery was not significantly different between groups. The data indicate that alfentanil-induced sedation and ventilatory depression are not significantly affected by the subsequent administration of ondansetron.
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PMID:Ondansetron does not affect alfentanil-induced ventilatory depression or sedation. 138 67

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

The purpose of this study was to determine the effects of reversal of sedation with flumazenil (F), in the presence or absence of opiates, on arterial oxygen saturation (SaO2) and end-tidal CO2 (ETCO2). Twenty-four patients undergoing surgery and epidural anaesthesia were studied. Twelve patients (Group A) were orally premedicated with diazepam and 0.1 mg.kg-1 morphine i.m. Intraoperative sedation consisted of midazolam 0.1 mg.kg-1 and pethidine 0.7 mg.kg-1 i.v. Twelve patients (Group B) were premedicated with diazepam and sedated intraoperatively with 0.1 mg.kg-1 midazolam. In the recovery room, six patients in each group were randomly allocated to receive 1 mg of flumazenil while the others were allowed to awaken spontaneously (control). Sedation (eyes open vs closed), SaO2, ETCO2, respiratory rate, blood pressure and pulse were non-invasively monitored for 90 min. Administration of flumazenil resulted in a statistically significant increase in the number of patients with eyes open in both groups at 5 min, lasting 15 min in Group A and 30 min in Group B patients. An increase in SaO2 from 15-45 min after injection of flumazenil was observed only in Group B. No significant difference between groups in any other parameter was found. We concluded that reversal of benzodiazepine (BZ) sedation with flumazenil improved SaO2 in patients sedated with only BZ; in the presence of BZ and opiates, flumazenil did not affect respiratory parameters.
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PMID:The respiratory effects of reversing midazolam sedation with flumazenil in the presence or absence of narcotics. 210 73

We studied the effect of nalbuphine on the ventilatory and occlusion pressure responses to carbon dioxide rebreathing in six healthy male volunteers (mean age 25.5 yr) in a single-blind laboratory study. On four separate days volunteers were assigned randomly to receive either placebo (0.9% sodium chloride) or three i.v. doses of nalbuphine (15, 30 and 60 mg 70 kg-1), followed 90 min later by naloxone 0.4 mg 70 kg-1. Duplicate rebreathing tests were performed and the mean intercept at PE'CO2 7 kPa and the slopes of the linear relationship between inspiratory minute ventilation (Vl) or occlusion pressure (P0.1) with PE'CO2 were measured. Nalbuphine significantly decreased the mean intercept of the Vl (P less than 0.01) and P0.1 (P less than 0.05) responses, but caused no changes in the slopes. No significant difference between the doses was noted, suggesting that an Effect maximum (E'max) for respiratory depression was reached with a dose of approximately 15 mg 70 kg-1. Naloxone was less effective in antagonizing the depression in Vl at the higher dose of nalbuphine. Similar P0.1 values were associated with the same inspiratory flow rate (1 litre s-1) before and after drug treatment, suggesting that nalbuphine acts centrally to depress ventilation. Sedation increased significantly following each dose of nalbuphine (P less than 0.001). No demonstrable difference between the doses was shown, suggesting an Effect maximum (E'max) for sedation was reached at about 15 mg 70 kg-1. Administration of nalbuphine was associated with pain at the injection site, dizziness, dreaming, nausea and vomiting. Cardiovascular stability was maintained in all subjects.
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PMID:Effect of nalbuphine hydrochloride on the ventilatory and occlusion pressure responses to carbon dioxide in volunteers. 250 65

Traditional methods of monitoring sedated pediatric dental patients have major shortcomings. This study evaluated the use of capnography in conjunction with pulse oximetry for monitoring children during conscious sedation for dental treatment. The specific purposes of the study were to determine if capnography would: (1) detect ventilatory changes that subsequently cause an oxyhemoglobin desaturation as detected by pulse oximetry; and (2) detect an airway obstruction. Ten pediatric dental patients (mean age 2 years, 10 months) were sedated with 75 mg/kg of chloral hydrate in strict accordance with the Guidelines for the Elective Use of Conscious Sedation, Deep Sedation, and General Anesthesia in Pediatric Patients of the American Academy of Pediatric Dentistry and the American Academy of Pediatrics (1985). All patients were monitored continuously using both capnography and pulse oximetry. Analysis of data obtained using these monitors revealed that specific end-tidal CO2 values were not predictive for subsequent oxyhemoglobin desaturations and that capnography was very accurate in detecting complete obstruction of the airway. Pulse oximetry revealed that all patients had mild oxyhemoglobin desaturations and that 50% had moderate desaturations.
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PMID:An investigation of capnography and pulse oximetry as monitors of pediatric patients sedated for dental treatment. 250 18

In 14 intubated, spontaneously breathing children with body weight (bw) ranging from 8.3 to 25.6 kg, the influence of midazolam 0.1 mg kg-1 i.m. (group M0.1, n = 7) and 0.2 mg kg-1 i.m. (group M0.2, n = 7) as premedication, on sedation, ventilation, ventilatory response to carbon dioxide and hormonal stress response was studied in connection with minor surgical procedures during halothane anaesthesia. The concentrations of catecholamines, ACTH and cortisol were measured immediately after induction, during undisturbed anaesthesia, during surgery and 15 min after the end of the surgical procedure. Sedation was better and plasma catecholamine concentrations during undisturbed anaesthesia were less in children receiving the larger dose of midazolam. During surgery and in recovery there were no differences in hormone concentrations. In recovery, the concentrations of all hormones were significantly greater compared with during undisturbed anaesthesia. During surgery, VE and respiratory rate were somewhat lower in group M0.2 while E' CO2 was similar. A dose dependent depression of the response to carbon dioxide was found. However, clinically, the ventilatory response to carbon dioxide after surgery was considered to be adequate in both groups.
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PMID:Ventilation, ventilatory carbon dioxide and hormonal response during halothane anaesthesia and surgery in children after midazolam premedication. 302 78

To assess the effects of isoflurane on chemical regulation of ventilation, we studied the ventilatory responses to (1) hyperoxic hypercarbia, (2) isocapnic hypoxaemia, and (3) a single half vital capacity breath of carbon dioxide 20 per cent in oxygen in 12 human subjects, awake and sedated or anaesthetized with isoflurane, 0.1 or 1.1 MAC. Sedation did not alter ventilation nor the ventilatory response to hypercarbia but reduced the responses to hypoxaemia and to the half vital capacity breath of CO2. Anaesthesia reduced ventilation and the response to hypercarbia and nearly abolished the responses to hypoxaemia and to the breath of CO2. The results indicate that isoflurane reduces ventilatory responses to several chemical drives and that it selectively impairs those responses mediated by peripheral chemoreceptors. In these respects, isoflurane is similar to halothane and enflurane.
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PMID:Chemical regulation of ventilation during isoflurane sedation and anaesthesia in humans. 641 54

Sedation elicited by some centrally acting antihypertensive agents may interfere with respiratory control, and by selectively inhibiting upper airway dilating muscle activity it may facilitate obstructive sleep apnea. Autoradiographic studies with [125I]p-iodoclonidine in the presence of 10 microM epinephrine to block alpha 2-adrenergic sites or 100 nM moxonidine to mask I1-imidazoline sites show that both I1- as well as alpha 2-sites are localized in putative chemosensory areas of the rostral ventrolateral medulla in the cat. We sought to determine the effect of activating I1 and alpha 2-receptors on central chemosensitivity by using moxonidine as a selective I1 agonist, clonidine as a mixed I1/alpha 2 agonist, SK&F-86466 as a specific alpha 2-antagonist, and efaroxan as a mixed I1/alpha 2 antagonist. We recorded responses of phrenic, hypoglossal, and cervical sympathetic nerve activities to progressive hypercapnia after hyperventilation to apnea. Moxonidine (3-100 micrograms/kg i.v.) caused dose-dependent decreases in tonic cervical sympathetic nerve activity and blood pressure, but had no effect on the CO2 threshold (after 30 or 100 micrograms/kg moxonidine, phrenic nerve activity reappeared at 5.8 +/- 0.2% CO2 versus 5.6 +/- 0.3% CO2 in control). Following moxonidine, the slope of the steep portion of the CO2 response tended to increase (10.3 +/- 1.8 versus 7.3 +/- 0.9). Peak phrenic nerve activity was comparable to control at 7.5% CO2 (20 +/- 2 U in control) and at 9.5% CO2 (30 +/- 3 versus 27. +/- 2 U). Similarly, the response of hypoglossal and inspiratory phasic cervical sympathetic nerve activity to a progressive CO2 rise was not affected by moxonidine. By contrast, clonidine in the same doses decreased CO2 sensitivity, because the CO2 threshold was elevated from 5.3 +/- 0.5% to 6.7 +/- 0.4% (p < 0.001). The slope of the CO2 response was decreased from 9.7 +/- 1.9 to 7.4 +/- 1.3 (p = 0.05). Peak phrenic nerve activity was reduced at 7.5% CO2 (11 +/- 5 versus 25 +/- 2 U; p < 0.05) and at 9.5% CO2 (21 +/- 4 versus 33 +/- 2 U; p = 0.06). Clonidine selectively inhibited the response of hypoglossal nerve activity to CO2. The depressive effects of clonidine were reversed by alpha 2-blockade with SK&F-86466 (0.5 or 1 mg/kg). Inspiratory phasic cervical sympathetic nerve activity increased after SK&F-86466 in parallel with phrenic and hypoglossal nerve activity, but the tonic component of cervical sympathetic nerve activity and blood pressure increased only transiently.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of I1-imidazoline receptor activation on responses of hypoglossal and phrenic nerve to chemical stimulation. 767 59

Sedation may be used in intensive care and emergency medicine to improve the oxygen demand/delivery ratio. The influence of sedation has most frequently been investigated in a dose-related manner. The aim of the present study was to determine the effect-related influence of different sedatives on oxygen uptake (VO2) in relation to defined resting conditions. METHODS. Forty ASA I patients who had to undergo a minor surgical procedure were investigated 1.5 h before surgery at basal energy-expenditure measurement conditions. One of the following substances was given with a preset bolus rate in a double-blind, randomised order until a defined level of sleep or side effects was encountered: propofol (n = 8), midazolam (n = 8), thiopentone (n = 8), sodium chloride (n = 8), and fentanyl (n = 8). The sleep level was defined as sluggish response to a loud voice or tapping on the forearm. The variables VO2, carbon dioxide elimination (VCO2), end tidal CO2 (p(et)CO2), oxygen saturation (SaO2), heart rate, systemic blood pressure, skin temperature, and skin resistance on the sole of the foot were documented on-line on a computer. All variables were compared using differences of averages from 10-min periods before and after sedation during which the VO2 was minimal. RESULTS. The mean VO2 before sedation was 264 +/- 60 ml/min, and the measured energy expenditure did differ by -0.2% (+/- 14%) from mean predicted values using the Harris-Benedict equation. The VO2 was reduced by 15 +/- 2% with propofol, by 12 +/- 8% with midazolam, and by 10 +/- 5% with thiopentone. This was statistically significant compared to placebo treatment, as was the difference between propofol and thiopentone effects. All patients in these groups reached the defined sleep level, which was not achieved by the placebo and fentanyl groups. Placebo treatment changed the VO2 by 0.1% (+/- 2%). Fentanyl increased the VO2 by 5% (+/- 8%), which did not reach significance. In the fentanyl group the bolus application had to be stopped at a p(et)CO2 of 50 mm Hg in all patients. In the propofol, midazolam, and thiopentone groups the phasic changes of skin resistance were reduced to zero and the skin temperature increased from 27 +/- 2 degrees C to 32 +/- 2 degrees C. The fentanyl group showed an increase in changes of skin resistance without changes in temperature. CONCLUSIONS. Sleep induced by propofol, midazolam, or thiopentone to a clinically maximal desirable level in spontaneously breathing patients reduced VO2 by 10% to 15%. This level of sedation did not induce a relevant change in P(et)CO2 or SaO2. The effect of propofol appeared to be the most pronounced and least variable. This may be attributable to a more pronounced reduction in single-organ VO2 or to an undetected difference in level of sedation. Fentanyl did, in contrast to most publications on opioid effects, seem to increase VO2. Underlying mechanisms may be sought in an increased rate-pressure product and sympathetic activity on the basis of hypercapnia and changes in muscle tension.
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PMID:[The effect of sedation on oxygen uptake during spontaneous breathing]. 834 51


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