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[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.

Administration, Oral↗

[Optimizing anesthesiologic premedication with reference to biopsychological theories. Exemplified by the effect of dipotassium clorazepate and zolpidem in combination with promethazine].

UNLABELLED: The following double-blind randomized placebo-controlled study dealt with three questions: 1. Are differentiated psychometric test systems suitable measuring emotions before anaesthesia? 2. What are the effects of different doses of zolpidem (8.03 mg vs. 16.06 mg) compared with dipotassiumclorazepat (10 mg vs. 20 mg) on emotions in premedication? 3. Is the combination with Promethazin suggestive? METHOD: 320 patients were randomly assigned to different regimes of preanaesthetic medication. As primary premedication they received either zolpidem 8.03 mg or zolpidem 16.06 mg or dipotassium clorazepate 10 mg or dipotassium clorazepate 20 mg or placebo. The secondary premedication was either promethazine 50 mg or placebo. The tablets/dragees were given in the evening before surgery (09.00 p.m.-10.00 p.m.). Every cell of the 5 x 2-factorial design contained 16 men and 16 women. Emotions were measured by a multidimensional rating scale, comprising the aspects elated mood, anxiety, hostility, deactivation, vigilance and introversion. In addition, somatic symptoms and the quality of sleep were measured. Statistics were performed using multivariate analysis of variance. RESULTS: No differing effects of zolpidem and dipotassium clorazepate on preoperative mood were found. There was also no difference compared with placebo. Compared with placebo, promethazin leads to greater deactivation. Specific emotions were not affected. In somatic aspects there was a greater amount of cholinergic effects under promethazine, which was mainly expressed by a higher intensity of a dry mouth and weakness in general. Compared with placebo all of the tested drugs led to a better quality of sleep. CONCLUSIONS: Using multidimensional rating scales and considering emotions as a multifactorial construct, the study shows no different effects of benzodiazepines or benzodiazepin-like drugs on preoperative mood. No differences were also found on comparing these drugs with placebo. However, a better quality of sleep was seen under zolpidem and dipotassium clorazepate compared with placebo. The study shows that a combination with promethazine is recommended, because promethazine has a selective deactivating effect. The study stresses the significance of multidimensional rating scales for the measurement of emotions before anaesthesia.

Adult↗

[0.15 mg clonidine as oral premedication in retrobulbar anesthesia].

BACKGROUND: In the present clinical study, oral premedication of 0.15 mg clonidine has been explored with view to anxiolytic effects and physiological stress parameters. METHODS: The study involved 44 patients of ASA-class I-III, all scheduled to undergo ophthalmological surgery under retrobulbar anesthesia (RBA). One hour before RBA 22 patients received 0.15 mg clonidine and 22 patients placebo p.o. The following parameters were assessed at different times perioperatively: oxygenation (SpO2), heart rate, blood pressure, intraocular pressure and anxiety. Anxiolysis was determined using the Erlanger Anxiety Scale. RESULTS: There were no significant differences among the groups in SpO2 and heart rate. Significantly decreased blood pressures were measured after clonidine premedication (p < 0.01). In contrast to clonidine after placebo the preoperative anxiety increased. Right before operation anxiety was decreased significantly (p < 0.01) by clonidine compared to placebo. CONCLUSIONS: In our opinion, oral clonidine (0.15 mg) is useful for premedication of surgery under RBA.

Administration, Oral↗

Effect of dose and premedication on induction complications with etomidate.

The induction characteristics of etomidate, a new i.v. hypnotic agent, were studied in 400 patients. Two hundred were premedicated with atropine and anaesthesia was induced with 0.2, 0.25, 0.3 or 0.35 mg/kg of etomidate. The remainder received one of four standard premedications and anaesthesia was induced with etomidate 0.3 mg/kg. Involuntary muscle movements occurred in more than 60% of patients receiving atropine alone. The frequency was reduced in the second group, but remained unacceptable in over 8% of patients. The incidence of other excitatory phenomena, such as cough and hiccup, was 10% approximately. Cardiovascular changes were minimal and no serious allergic phenomena were observed. Nausea and vomiting occurred after surgery in up to 30% of patients and was unrelated to the dose of etomidate or to premedication. Pain on injection occurred in up to 80% of patients when the drug was injected into small peripheral veins and occurred in more than 7% when using more normal veins.

Adult↗

Effect of premedication on etomidate anaesthesia.

The effect of premedication upon the induction of anaesthesia with etomidate was studied in 74 adult patients undergoing elective orthopaedic surgery. Premedication with fentanyl plus atropine or with diazepam plus atropine decreased the frequency of involuntary muscle movements without modifying the pattern of the circulatory effects of etomidate, although fentanyl increased the frequency of apnoea. Pain at the site of injection was not modified by premedication.

Adolescent↗

Comparison of three benzodiazepines for oral premedication in minor gynaecological surgery.

Diazepam 10 and 20 mg, lorazepam 2.5 and 5.0 mg, flunitrazepam 1 and 2 mg, and a placebo, were compared in a randomized double-blind controlled trial as oral premedication for 210 patients undergoing minor gynaecological surgery. Flunitrazepam 1 mg and lorazepam 2.5 mg were superior to placebo (P less than 0.001 and P less than 0.05 respectively) in relieving patient anxiety when assessed by a trained observer 60 min after premedication. Flunitrazepam 1 mg also produced more drowsiness (P less than 0.01) than the placebo. Comparisons of other low-dose benzodiazepine groups with the placebo, and of the large dose with the small dose of each drug revealed no significant changes in anxiolysis or drowsiness. Dizziness and prolonged drowsiness were not apparent with low-dose flunitrazepam. The data suggests that flunitrazepam 1 mg offers advantages over placebo, diazepam 10 mg and lorazepam 2.5 mg for routine oral premedication in minor gynaecological surgery.

Adolescent↗

Influence of premedication on the sympathetic and endocrine responses and cardiac arrhythmias during halothane anaesthesia in children undergoing adenoidectomy.

The occurrence of cardiac arrhythmia was investigated in 80 children during halothane anaesthesia for adenoidectomy. Two different premedications were studied. Forty children (group A) were premedicated with diazepam 5 mg rectally and atropine 0.3-0.4 mg sublingually and 40 (group B) received a rectal solution including diazepam 0.5 mg kg-1, morphine 0.15 mg kg-1 and hyoscine 0.01 mg kg-1. In 17 of these children (nine in group A and eight in group B) plasma concentrations of catecholamines, ACTH and corticosteroids were measured. In group A the mean plasma concentration of catecholamines increased more than 300% during surgery, while it was virtually unchanged in group B (P less than 0.01). Plasma concentrations of ACTH, cortisol and 17-alpha-hydroxyprogesterone were also greater in group A than in group B. The occurrence of ventricular arrhythmias in group A was significantly more frequent (20.0%) than in group B (2.5%) (P less than 0.05). It was concluded that in these two comparable groups of patients ventricular arrhythmia during halothane anaesthesia was almost eliminated by the use of more effective premedication, as a result of decreases in the sympathetic and endocrine responses to surgery.

Adenoidectomy↗

Comparison of the cognitive effects of premedication with hyoscine and atropine.

An investigation was carried out comparing the nature and duration of the cognitive effects of atropine and hyoscine. Thirty patients undergoing a minor gynaecological operation were randomly assigned to one of three groups to receive hyoscine, atropine or placebo as premedication. A battery of psychological tests was administered before premedication, 30 min after premedication, and 1 and 3 h following operation. The tests included orientation questions, simple tasks such as reciting the alphabet, memory tests, a reaction-time test and two tests of visuo-motor co-ordination. The results showed that hyoscine had detrimental effects on memory and on motor tasks compared with placebo, while atropine did not. In addition, the effects on motor performance had not disappeared 3 h after operation.

Adult↗

Influence of premedication on lignocaine-induced acute toxicity and plasma concentrations of lignocaine.

The effects were studied, in eight healthy volunteers, of premedication with diazepam 0.14 mg kg-1 by mouth or hyoscine 6 micrograms kg-1 + morphine 0.2 mg kg-1 i.m., or no premedication, on toxic symptoms and plasma concentrations after rapid i.v. injection of lignocaine 1 mg kg-1. The alpha 1-acid glycoprotein (AAG) and albumin plasma protein fractions were assessed. A variety of mild central nervous system (CNS) symptoms were experienced after the bolus of lignocaine. However, there was no correlation between premedication and degree of severity or number of CNS symptoms. The highest single arterial plasma concentration of lignocaine was 11.0 micrograms ml-1, 1 min after injection. There was no correlation between plasma concentration of lignocaine and occurrence of CNS symptoms. Furthermore, there was no correlation between AAG or albumin plasma concentrations and lignocaine plasma concentrations.

Adult↗

Clonidine premedication improves metabolic control in type 2 diabetic patients during ophthalmic surgery.

BACKGROUND: In stressful conditions, increasing blood glucose concentrations are closely related to an increase in catecholamines and cortisol release. Clonidine, a centrally acting alpha(2)-adrenoceptor agonist, has neuroendocrine effects, including inhibition of sympathoadrenal activity. We therefore evaluated the effect of clonidine on blood glucose control and insulin requirements during ophthalmic surgery when given as premedication in type 2 diabetic patients. METHODS: After randomization, patients were premedicated with clonidine or flunitrazepam (control). Patients were given insulin by continuous i.v. infusion to maintain blood glucose in the range 5.5-11.1 mmol litre(-1). Blood glucose concentrations were measured every 15 min during surgery, and hourly for 6 h after surgery. Plasma C-peptide and counter-regulatory hormones were also measured. RESULTS: Glycaemia was significantly lower in the clonidine group (P<0.01) and the median amount of insulin administered was significantly reduced: clonidine group 9.0 (interquartile range 5.1) units; control 18.6 (10.2) units; P<0.01). Plasma catecholamine concentrations were lower in patients given clonidine (P<0.05) but there was no difference in cortisol concentrations. CONCLUSION: Premedication of type 2 diabetic patients with clonidine 90 min before surgery improves blood glucose control and decreases insulin requirements during ophthalmic surgery.

Aged↗

Agitation and changes of Bispectral Index and electroencephalographic-derived variables during sevoflurane induction in children: clonidine premedication reduces agitation compared with midazolam.

BACKGROUND: This double-blind randomized study was undertaken to assess agitation, Bispectral Index (BIS) and EEG changes during induction of anaesthesia with sevoflurane in children premedicated with midazolam or clonidine. METHODS: Children were allocated randomly to receive rectal midazolam 0.4 mg kg(-1) (n=20) or oral clonidine 4 microg kg(-1) (n=20) as premedication. Rapid induction of anaesthesia was achieved with inhalation of sevoflurane 8% in nitrous oxide 50%-oxygen 50%. After tracheal intubation, the children's lungs were mechanically ventilated and the inspired sevoflurane concentration was adjusted to achieve an end-tidal fraction of 2.5%. The EEG and BIS were recorded during induction until 10 min after tracheal intubation. The EEG was analysed using spectral analysis at five points: baseline, loss of eyelash reflex, 15 s before the nadir of the BIS (BIS(nadir)), when both pupils returned to the central position (immediately before intubation), and 10 min after intubation. RESULTS: Agitation was observed in 12 midazolam-treated and five clonidine-treated patients (P=0.05). At baseline, EEG rhythms were slower in the clonidine group. Induction of anaesthesia was associated with similar EEG changes in the two groups, with an increase in total spectral power and a shift towards low frequencies; these changes were maximal around the end of the second minute of induction (BIS(nadir)). When the pupils had returned to the central position, fast EEG rhythms increased and BIS was higher than BIS(nadir) (P<0.05). In both groups, agitation was associated with an increase in slow EEG rhythms at BIS(nadir). CONCLUSIONS: Compared with midazolam, clonidine premedication reduced agitation during sevoflurane induction. During induction with sevoflurane 8% (oxygen 50%-nitrous oxide 50%), the nadir of the BIS occurred at the end of the second minute of inhalation. Agitation was associated with a more pronounced slowing of the EEG rhythms at BIS(nadir) compared with inductions in which no agitation was observed. The BIS may not follow the depth of anaesthesia during sevoflurane induction in children.

Adjuvants, Anesthesia↗

Comparison of the incidence of complications at induction and emergence in infants receiving oral atropine vs no premedication.

We studied 120 patients less than 1 yr of age, allocated randomly to receive atropine 40 micrograms kg-1 orally 1 h before operation (group A) or no premedication (group B). All patients underwent a standardized anaesthetic, including inhalation induction with halothane followed by atracurium 0.5 mg kg-1, tracheal intubation and positive pressure ventilation. Monitoring during anaesthesia included heart rate, arterial oxygen saturation, temperature and airway conditions at induction and emergence. The incidence of a decrease in arterial oxygen saturation to 94% or less at induction and recovery was similar in both groups (30.5% at induction, 39% at extubation in group A; 31% at induction, 41% at extubation in group B). There were significantly more airway complications in group B both at induction and emergence (25% and 49%, respectively, compared with 9% and 25% in group A; P < 0.015). Mean heart rate at induction and in the peroperative period was significantly higher in the group receiving atropine (P < or = 0.001). There was an increased incidence of bradycardia (decrease in heart rate of > or = 20%) at induction in the non-premedicated group (23% in group B compared with 10% in group A), but this was not statistically significant. We conclude that the incidence of airway complications at induction and emergence was reduced by orally administered atropine premedication.

Anesthesia Recovery Period↗

Oral clonidine premedication enhances the pressor response to ephedrine during spinal anesthesia.

UNLABELLED: Clonidine premedication enhances the pressor effects of ephedrine in awake and anesthetized patients. To test the hypothesis that clonidine augments the pressor response to ephedrine during spinal anesthesia, 48 ASA physical status I or II patients were randomly assigned to either the clonidine group (n = 23), receiving oral clonidine approximately 5 microg/kg 90 min before spinal anesthesia, or the control group (n = 25), receiving no clonidine. Spinal anesthesia was performed at either the L2-3 or the L3-4 interspace using 0.5% hyperbaric tetracaine solution 1.4-3.0 mL. Blood pressure (BP), heart rate, and the upper dermatomal level of analgesia were determined at 1-min intervals with the patient in the supine position after tetracaine injections. When systolic BP decreased to <80% of the prespinal value or <100 mm Hg, IV ephedrine 0.2 mg/kg was administered as a bolus. There were no differences in the duration until the first dose of ephedrine after tetracaine injections, and the upper level of analgesia between groups (control group 8.5+/-3.7 min, T5; clonidine group 7.7+/-2.7 min, T6). Although prespinal and preephedrine BP values were higher in the control group, the magnitude of increases in mean BP after ephedrine was significantly greater in the clonidine group (P < 0.05). We conclude that oral clonidine premedication augments the pressor response to IV ephedrine during spinal anesthesia. IMPLICATIONS: The pressor effect of ephedrine is enhanced in patients given oral clonidine premedication during spinal anesthesia.

Administration, Oral↗

Premedication with midazolam delays recovery after ambulatory sevoflurane anesthesia in children.

UNLABELLED: We studied the effect of oral premedication with midazolam on the recovery characteristics of sevoflurane anesthesia in small children. In a randomized, double-blinded study, 60 children (1-3 yr, ASA physical status I or II) undergoing ambulatory adenoidectomy received either midazolam 0.5 mg/kg (Group M) or placebo (Group P) PO approximately 30 min before the induction of anesthesia. All children received atropine 0.01 mg/kg IV and alfentanil 10 microg/kg IV before the induction of anesthesia with sevoflurane up to 8 vol% inspired concentration in N2O 67% in O2. Tracheal intubation was facilitated with mivacurium 0.2 mg/kg. Anesthesia was continued with sevoflurane adjusted to maintain hemodynamic stability. In the postanesthesia care unit, predetermined recovery end points (emergence, recovery, discharge) were recorded. A pain/ discomfort scale was used to determine the quality of recovery. A postoperative questionnaire was used to evaluate the well-being of the patient at home 24 h after surgery. Emergence (spontaneous eye opening), recovery (full points on the modified Aldrete scale), and discharge were achieved later in Group M than in Group P (15+/-6 vs. 11+/-3 min [P = 0.002], 25+/-17 vs. 16+/-6 min [P = 0.01], and 80+/-23 vs. 70+/-23 min [P = 0.03]). Side effects, postanesthetic excitement, and analgesic treatment did not differ significantly between groups. At home, more children in Group P (30%) experienced disturbed sleep during the night compared with those in Group M (4%) (P = 0.007). IMPLICATIONS: In this randomized, double-blinded, placebo-controlled study, premedication with midazolam 0.5 mg/kg PO delayed recovery in children 1-3 yr of age after brief (<30 min) sevoflurane anesthesia. Except for more peaceful sleep at home, premedication did not affect the quality of recovery.

Adenoidectomy↗

Premedication and high-dose fentanyl anesthesia for myocardial revascularization: a comparison of lorazepam versus morphine-scopolamine.

Using a randomized double-blind placebo-controlled experimental protocol, the authors compared two premedication regimens in 42 patients undergoing elective myocardial revascularization. Group L patients (n = 23) received lorazepam 0.06 mg/kg po 90 min preoperatively, while group M patients (n = 19) received morphine 0.1 mg/kg im, plus scopolamine 0.006 mg/kg im 60 min preoperatively. Anesthesia was induced with fentanyl 100 micrograms/kg and atracurium 0.50 mg/kg administered over 10 min. The treatment groups did not differ significantly with respect to the degree of sedation or anxiolysis achieved, or the rapidity of induction with fentanyl. Premedication significantly influenced the hemodynamic response to anesthetic induction. Hemodynamics were stable post-induction in group M, but cardiovascular depression was noted in group L. Control heart rate (HR) was lower in group L. The HR, arterial pressure, and cardiac index were significantly lower, following both induction and intubation, in group L. Following sternotomy hemodynamics were identical in both groups. Serum fentanyl concentration was significantly higher during intubation in group L, probably secondary to the pharmacokinetic consequences of a decreased CI. New electrocardiographic evidence of myocardial ischemia did not occur in either group. Based on their findings with fentanyl-at-racurium, and their review of the literature, the authors speculate that premedication exerts a significant hemodynamic effect during induction with other narcotic-relaxant combinations.

Anesthesia, Intravenous↗

Drug interactions with sufentanil. Hemodynamic effects of premedication and muscle relaxants.

Induction of anesthesia with synthetic opioids is occasionally accompanied by undesirable hemodynamic changes such as tachycardia and hypertension, or bradycardia and hypotension. We hypothesized that drug interactions cause many of these adverse responses. Therefore, we conducted a randomized double-blind study to investigate the interactive effect of premedication and muscle relaxants on the hemodynamic response to induction with intravenous (iv) sufentanil 10 micrograms.kg-1. Eighty patients with left ventricular ejection fraction greater than or equal to 0.40, undergoing elective coronary artery surgery, were premedicated with either morphine 0.1 mg.kg-1 and scopolamine 6 micrograms.kg-1 intramuscularly, or lorazepam 60 micrograms.kg-1 orally, and paralyzed with either pancuronium 0.1 mg.kg-1 or vecuronium 0.1 mg.kg-1 iv. The four treatment groups were SP (morphine-scopolamine + pancuronium), LP (lorazepam + pancuronium), SV (morphine-scopolamine + vecuronium), and LV (lorazepam + vecuronium). Hemodynamics were recorded at three time periods: 1) control, 2) induction, and 3) intubation. Premedication-relaxant interactions significantly affected hemodynamics. In group SP, mean heart rate (HR) increased significantly on induction (56 +/- 11 to 69 +/- 13 beats.min-1), while mean arterial pressure (MAP) and cardiac index (CI) were unchanged. HR, MAP, and CI were significantly higher after induction in group SP compared to the other three groups. In group LP, mean HR increased less than in group SP (56 +/- 8 to 62 +/- 14 beats.min-1), whereas MAP and CI declined significantly. In group SV, HR and CI were unchanged, but MAP declined significantly. In group LV, HR was stable, whereas both MAP and CI declined significantly. The incidence of pharmacologic interventions during the study period also differed significantly among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Volume and pH of gastric contents following anticholinergic premedication.

The effects of anticholinergic premedication with 1.0 mg atropine, 0.5 mg hyoscine and 0.2 mg glycopyrronium on volume and pH of gastric contents were studied and compared with a group receiving no anticholinergic premedication. The antisialogogue effects were also compared. Though the groups receiving atropine and glycopyrronium had the lowest mean aspirated volume and the highest mean pH respectively there was no essential difference between the various groups receiving anticholinergic premedication. However, the pH values were above 2.5 in the majority of these patients in comparison with the control group. The antisialogogue effects of the three anticholinergic drugs were similar.

Adult↗

A comparison of triazolam and diazepam as premedication agents for minor gynaecological surgery.

Triazolam 0.25 mg, diazepam 10 mg and placebo were compared in a randomized double-blind trial of oral premedication in 90 patients undergoing minor gynaecological surgery. Both triazolam and diazepam produced a significant sedative effect as measured by patient self assessment linear analogue scales but only diazepam was more anxiolytic than placebo. Psychomotor performance assessed by the letter-search test at 3 and 6 hours after awakening showed a decrement in performance in patients receiving triazolam at 3 hours compared with the two other groups. Triazolam was shown to have a pronounced amnesic effect and whilst it might be used for premedication, its lack of anxiolysis coupled with a significant impairment of psychomotor performance at 3 hours after awakening, render the drug unsuitable for premedication in the short stay patient.

Adult↗