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The effect of acutely elevated serum magnesium on the CNS and cardiac toxicity of bupivacaine was studied. Anesthesia was induced in mongrel dogs with thiopental, 25 mg/kg, and ventilation was controlled. Sedation was maintained with fentanyl (25 micrograms/kg bolus and 5 micrograms.kg-1h-1) and pancuronium (0.15 mg/kg bolus and 0.05 mg.kg-1h-1) provided paralysis. Two hours after the thiopental bolus, all animals received an intravenous (iv) infusion of bupivacaine (1 mg.kg-1 min-1). The control group (5 animals) received bupivacaine only. The Mg++ group (5 animals) received MgSO4 140 mg/kg iv and 80 mg.kg-1 h-1 15 min prior to beginning the bupivacaine infusion. Lead II ECG, cardiac hemodynamics, and two-channel EEG were continuously monitored. Serum magnesium concentrations in the Mg++ group rose from 0.67 mM (1.3 mEq/L) to 2.42 mM (4.8 mEq/L). The bupivacaine infusion caused PR and QRS interval prolongation in both groups, but QRS widening was greater in the control group. QT interval corrected for heart rate (QTIc) lengthened only in the control group. A depression of left ventricular stroke work index (LVSWI) occurred to an equal extent in both groups. The seizure dose of bupivacaine was not different between the two groups: 12.9 +/- 2.3 (SEM) mg/kg in the control group and 13.9 +/- 2.5 mg/kg in the Mg++ group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of magnesium sulfate administration on cerebral and cardiac toxicity of bupivacaine in dogs. 230 66

Two groups of six patients who had undergone major maxillofacial surgery and who required intermittent positive pressure ventilation, analgesia and sedation for about 48 hours postoperatively were studied. Analgesia in the postoperative period was maintained by an infusion of fentanyl 0.034 micrograms/kg/minute. Sedation was maintained with an intravenous infusion of etomidate such that the patients slept but opened their eyes when addressed and obeyed commands. An assay method was developed which enabled the measurement of plasma concentration of etomidate for periods of up to 24 hours after stopping the infusion. The steady state plasma concentration associated with the technique which produced the required degree of sedation was found to be 158 micrograms/litre (SEM 36). Etomidate exhibited linear pharmacokinetics and the decrease in plasma concentration of etomidate after stopping the infusion was consistent with a three-compartment pharmacokinetic model. All the patients recovered within 1 hour of stopping the infusion. The use of results obtained from the first group of six patients enabled a dosage regimen to be calculated that used a two stage infusion. This regimen enabled a reduction in the time taken to establish the appropriate degree of sedation in the second group of six patients. The two-stage infusion technique provides a means of rapid sedation and of maintaining a suitable clinical response for the prolonged periods that may be necessary when patients are transferred to an intensive therapy unit.
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PMID:Plasma concentrations of etomidate during an intravenous infusion over 48 hours. 686 54

The effects of oral guanfacine were examined in six patients with essential hypertension. Guanfacine caused a substantial fall in both lying and standing systolic and diastolic blood pressure. The fall in pressure was evident by 6 hr, maximal by 10 to 12 hr, and lasted as long as 36 hr. In four patients satisfactory blood pressure control throughout the day was achieved during inpatient administration with single daily doses of 2 to 4 mg in the evening. The other two patients required twice-daily dosing for optimal control of blood pressure. There was no evidence of tolerance to the hypotensive effect. Sedation and xerostomia were apparent after the first dose but did not limit dose titration. Guanfacine lowered lying and standing plasma norepinephrine; this continued on long-term dosing. Urinary catecholamines were reduced from 59.21 +/- 17.24 (mean +/- SEM) to 28.91 +/- 4.20 micrograms/24 hr after 7 days of treatment. The hemodynamic effects, side effects, and biochemical evidence of reduced sympathetic activity after guanfacine resembled the centrally acting antihypertensive clonidine, although guanfacine appeared to have a longer duration of action.
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PMID:Effects of single and multiple doses of guanfacine in essential hypertension. 700 28

Sedation is routinely required for successful Magnetic Resonance imaging in infants and children. Five hundred and ninety-six paediatric patients (270 female and 326 male, age (mean +/- SD) 41 +/- 30 months and weight 14.8 +/- 6.5 kg) entered an open, non-comparative, prospective study to assess oral chloral hydrate sedation in a large and homogeneous paediatric population undergoing Magnetic Resonance imaging. Chloral hydrate syrup 70 mg/ml was administered 20-40 min prior to the procedure. Effective sedation was reached in 94.1% with a total dose (mean +/- SEM) of 68 +/- 1 mg/kg (range 20-170 mg/kg). Statistical analysis of sedation failures vs. successful examinations after the total dose showed significant differences for dose (62 +/- 4 vs. 69 +/- 1 mg/kg; P < 0.05), age (64 +/- 7 vs. 40 +/- 1 months; P < 0.001) and weight (19.8 +/- 1.5 vs. 14.5 +/- 0.0 kg; P < 0.001). Effectiveness fell to around 80% in children with encephalic white matter alterations, medullary tumours or syringohydromyela (P = 0.07). The mean time of onset of sedation was 26 +/- 1 min, and the mean time to spontaneous awakening after the completion of the Magnetic Resonance examination was 38 +/- 2 min. Fifty-nine children (9.9%) experienced adverse reactions, with nausea and vomiting being the most common (n = 41), followed by nervousness and unusual excitement (n = 6). Discriminant function analysis identified age and total dose as the quantitative variables helping to differentiate between sedation failures and satisfactory examinations (sensitivity = 0.73, and specificity = 0.61; r = 0.20, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oral chloral hydrate provides effective and safe sedation in paediatric magnetic resonance imaging. 798 2

Limited data support the use of first-generation antihistamines for treatment of the common cold. The purpose of this study was to test the effectiveness of clemastine fumarate, a first-generation antihistamine, for treatment of sneezing and rhinorrhea associated with naturally occurring common colds. Four hundred three subjects (202 clemastine fumarate recipients and 201 placebo recipients) who reported new onset (< 24 hours) of cold symptoms that included rhinorrhea or sneezing were studied. At baseline (day 1), the mean symptom-severity scores +/- SEM for the clemastine fumarate and placebo groups were not significantly different. The mean rhinorrhea-severity score +/- SEM was not different on day 2; however, on day 3, the mean rhinorrhea-severity score +/- SEM was 1.02 +/- 0.07 for the clemastine fumarate group and 1.39 +/- 0.07 for the placebo group (P < .001). This treatment effect persisted on day 4. A significant effect on sneezing was noted on days 2-4. Sedation occurred in 14% of the clemastine fumarate-treated subjects and 1.5% of the placebo-treated subjects (P < .0001).
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PMID:Effectiveness of clemastine fumarate for treatment of rhinorrhea and sneezing associated with the common cold. 935 96

This study was carried out in order to determine if intravenous (i.v.) sedation with diazepam, at the time of procedure, made fibreoptic bronchoscopy more tolerable and if these perceptions persisted on later questioning. Methodology consisted of a sequential, parallel group design comparing sedation with no sedation for bronchoscopy in a tertiary referral hospital. Patient comfort and sedation desired for hypothetical repeat bronchoscopy were assessed both immediately and after at least 1 month. Patients who received sedation rated bronchoscopy as more comfortable (P = 0.01). Those who received sedation were also more likely to want no change in sedation if the bronchoscopy were repeated (P < 0.01). These differences were more evident at later questioning. Sedation was not associated with an increased complication rate but was associated with a prolonged recovery room stay (no sedation, 19.2 min (SEM 3.8) compared with sedation, 76.1 min (5.4), P < 0.001). In contrast to previous studies, our patients found bronchoscopy more comfortable with i.v. diazepam sedation. This was supported by patients who received sedation being less likely to want any change in future sedation if a repeat bronchoscopy were required. The benefit seen with sedation was more marked at later questioning supporting a previously postulated amnesic effect. However, sedation was associated with a prolonged room stay and potentially greater attendant cost.
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PMID:Patients prefer sedation for fibreoptic bronchoscopy. 969 14

Tramadol, a mixed mu-opioid agonist and a monoamine-reuptake blocking analgesic, has been supposed to have little effect on propulsive gastrointestinal motility. However, this has not been specifically studied in man. Following institutional approval, 18 human volunteers were given 50 mg of tramadol, tilidine/naloxone, and codeine, respectively, in a double-blind randomised cross-over design. Additionally, 12 further volunteers were given 100 mg of each opioid in a double-blind, randomised fashion, followed by measurement of gastrocoecal transit time. Gastrointestinal transit time was measured using the lactulose H(2)-breath test. A threefold increase in end-expiratory hydrogen when compared to the control value was considered the end point of gastrocoecal transit. At the low dose (50 mg) the three opioids did not differ significantly with regard to their effect on gastrointestinal motility. Gastrocoecal transit time was 90.8 (+/- 10.1 SEM) min for tramadol, 100.6 (+/- 9.8 SEM) min for tilidine/naloxone, and 104.2 (+/- 8.7 SEM) min for codeine. Doubling the dose of each opioid resulted in an increase in mean gastrocoecal transit, namely 97.8 (+/- 11.2 SEM) min for tramadol, 129.2 (+/- 12.2 SEM) min for tilidine/naloxone and 135.9 (+/- 9.2 SEM) min for codeine. The increase in gastrocoecal transit time was significant (P < 0.01) for high doses of tilidine/naloxone and codeine in contrast to the effect of the low doses. This lesser constipation effect may be due to the reduced affinity of tramadol to the mu-opioid receptor. Sedation was significantly higher for codeine after 50 mg (P < 0.05) and 100 mg (P < 0.005) than for tilidine/naloxone and tramadol. Vertigo was significantly higher after 50 mg (P < 0.05) and 100 mg (P < 0.005) of tilidine/naloxone and codeine than after tramadol. Perspiration was significantly higher after tramadol 100 mg (P < 0.005) than after tilidine/naloxone and codeine. Sedation is considered a typical symptom of analgesics interacting with centrally located opioid receptor sites. The higher incidence of perspiration after tramadol suggests that monominergic pathways may be involved in thermoregulation. In conclusion, the opioids tilidine/naloxone and codeine at the doses used significantly prolong gastrointestinal transit time in the high-dose range. Since tramadol does not induce a dose-related increase in gastrocoecal transit time, it may be a useful analgesic in patients who are prone to developing constipation during high-dose opioid therapy.
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PMID:[Constipation after tilidine/naloxone and tramadol in comparison to codeine. A dose response study in human volunteers]. 1503 43