Oral Temazepam Research Articles

Assessing the validity of eyelid parameters to detect impairment due to benzodiazepines.

Benzodiazepines impair driving ability and psychomotor function. Eyelid parameters accurately reflect drowsiness; however, the effects of benzodiazepines on these measures have not been extensively studied. The aim of this study was to investigate the effect of benzodiazepines on eyelid parameters and evaluate their accuracy for detecting psychomotor impairment. Eyelid parameters were recorded during a psychomotor vigilance task (PVT) and driving simulation over 2 days, baseline, and after 20-mg oral temazepam. The utility of eyelid parameters for detecting PVT lapses was evaluated using receiver operating characteristic curves, and cut-off levels indicating impairment (≥1 and ≥2 PVT lapses per min) were identified. The accuracy of these cut-off levels for detecting driving simulator crashes was then examined. PVT and driving simulator performance was significantly impaired following benzodiazepine administration (p < .05). Average eyelid closure duration (inter-event duration) was a reliable indicator of PVT lapses (area under the curve [AUC] of 0.87-0.90). The cut-off value of eyelid closure duration derived from PVT AUC was able to predict driving simulator crashes with moderately high sensitivity and specificity (76.23% and 75.00%). Eyelid parameters were affected by benzodiazepines and accurately detected the psychomotor impairment. In particular, eyelid closure duration is a promising real-time indicator of benzodiazepine impairment.

Effects of oral temazepam on slow waves during non-rapid eye movement sleep in healthy young adults: A high-density EEG investigation

Slow waves are characteristic waveforms that occur during non-rapid eye movement (NREM) sleep that play an integral role in sleep quality and brain plasticity. Benzodiazepines are commonly used medications that alter slow waves, however, their effects may depend on the time of night and measure used to characterize slow waves. Prior investigations have utilized minimal scalp derivations to evaluate the effects of benzodiazepines on slow waves, and thus the topography of changes to slow waves induced by benzodiazepines has yet to be fully elucidated. This study used high-density electroencephalography (hdEEG) to evaluate the effects of oral temazepam on slow wave activity, incidence, and morphology during NREM sleep in 18 healthy adults relative to placebo. Temazepam was associated with significant decreases in slow wave activity and incidence, which were most prominent in the latter portions of the sleep period. However, temazepam was also associated with a decrease in the magnitude of high-amplitude slow waves and their slopes in the first NREM sleep episode, which was most prominent in frontal derivations. These findings suggest that benzodiazepines produce changes in slow waves throughout the night that vary depending on cortical topography and measures used to characterize slow waves. Further research that explores the relationships between benzodiazepine-induced changes to slow waves and the functional effects of these waveforms is indicated.

Effects of oral temazepam on sleep spindles during non-rapid eye movement sleep: A high-density EEG investigation

Benzodiazepines are commonly used medications that alter sleep spindles during non-rapid eye movement (NREM) sleep, however the topographic changes to these functionally significant waveforms have yet to be fully elucidated. This study utilized high-density electroencephalography (hdEEG) to investigate topographic changes in sleep spindles and spindle-range activity caused by temazepam during NREM sleep in 18 healthy adults. After an accommodation night, sleep for all participants was recorded on two separate nights after taking either placebo or oral temazepam 15mg. Sleep was monitored using 256-channel hdEEG. Spectral analysis and spindle waveform detection of sleep EEG data were performed for each participant night. Global and topographic data were subsequently compared between temazepam and placebo conditions. Temazepam was associated with significant increases in spectral power from 10.33 to 13.83Hz. Within this frequency band, temazepam broadly increased sleep spindle duration, and topographically increased spindle amplitude and density in frontal and central-posterior regions, respectively. Higher frequency sleep spindles demonstrated increased spindle amplitude and a paradoxical decrease in spindle density in frontal and centroparietal regions. Further analysis demonstrated temazepam both slowed the average frequency of spindle waveforms and increased the relative proportion of spindles at peak frequencies in frontal and centroparietal regions. These findings suggest that benzodiazepines have diverse effects on sleep spindles that vary by frequency and cortical topography. Further research that explores the relationships between topographic and frequency-dependent changes in pharmacologically-induced sleep spindles and the functional effects of these waveforms is indicated.

Sedation for radiological imaging

To obtain high-quality CT and MRI scans, children may need to stay immobile in a particularly uncomfortable environment for a reasonable length of time. Although young infants may sleep after...

CASE REPORT

A 71-year-old woman, weighing 70 kg, presented for surgery to revise first the right and then the left femoral and acetabular cemented prostheses with uncemented hydroxy-apatite ceramic coated Furlong® components (Joint Replacement Instrumentation, London). Her medical history was of essential hypertension, stable angina pectoris and an uncomplicated myocardial infarction 5 years previously. There was no evidence of cardiac failure or cerebrovascular disease. Medications included metoprolol, glyceryl trinitrate spray and oral ferrous sulphate for 2 months before surgery. On examination her blood pressure was 130/70 mmHg with no signs of cardiac failure and no carotid bruits. Electrocardiogram revealed a left bundle–branch block, and the chest radiograph showed unfolding of the aorta with a normal cardiac shadow and lung fields. Urea and electrolytes were within normal limits and haemoglobin (Hb) was 141 g/litre (operation 1) and 140 g/litre (operation 2). The patient expressed a desire not to receive any blood or blood-related products at any time, and completed the requisite Jehovah's Witness documentation. It was agreed that she would undergo preoperative isovolaemic haemodilution and intraoperative salvage of red blood cells, maintaining continuity with her circulation at all times. On both occasions the patient was premedicated with oral temazepam 20 mg and a 5 mg glyceryl trinitrate skin patch. After inserting a radial arterial line, a total of 700 ml of blood was venesected into bags containing citrate for anticoagulation and kept in continuity with the patient's circulation. Blood pressure was maintained during venesection using two 3 mg ephedrine boluses before volume replacement with 1000 ml of Gelofusine® (Braun, Melsungen) was commenced. Anaesthesia was induced with thiopentone 200 mg and maintained with isoflurane and nitrous oxide in 40% oxygen. Muscle relaxation was achieved using vecuronium and the patient intubated after receiving alfentanil 0.5 mg. Her lungs were mechanically ventilated to an end tidal PaCO2 of 4.8–5.0 kPa. Intraoperative and postoperative analgesia was achieved on both occasions with a lumbar epidural catheter inserted at L1/2 interspace, using a continuous infusion of bupivacaine 1 mg/ml and fentanyl 2 μg/ml. Standard intraoperative monitoring included invasive blood pressure, central venous pressure and oesophageal temperature. A urethral catheter was inserted and body temperature maintained around 36°C using intravenous fluid warmers and a Warm Touch® (Gaymar, Hamburg). Intraoperative red blood cell salvage was achieved with a Haemonetics Cell Saver®5 (Haemonetics Corporation, Massachusetts), set up with a continuous circuit from the surgical sucker, through the filtration and reservoir units to an intravenous line in the patient using normal saline as a primer. Intraoperative systolic blood pressure was maintained between 90–100 mmHg. Surgery involved meticulous removal of all cement using cement splitting and extracting instruments under image intensifier control. Finally granulation tissue between cement and bone was curetted away to expose bleeding cancellous bone. There were no unexpected surgical complications. Intraoperative blood loss totalled 1250 ml (operation 1), and 1100 ml (operation 2). A total of 2000 ml of colloid was infused after isovolaemic haemodilution and before the completion of surgery, at which time an arterial blood gas sample revealed no significant metabolic acidosis on either occasion. After wound closure a total of 500 ml of Cell Saver®5 infusate with an estimated haematocrit of 0.55 was transfused. Finally the two 350 ml bags of autologous blood were infused slowly over the next few hours. Following extubation the patient was transferred to intensive care for overnight monitoring and continuous postoperative epidural analgesia. Investigations included full blood count, urea and electrolytes, coagulation profile, and arterial blood gases. Serial 12-lead electrocardiograms and cardiac enzymes revealed no evidence of myocardial ischaemia or infarction on either occasion. Demonstrable postoperative blood losses totalled approximately 500 ml for each operation. The lowest recorded Hb was 80 g/litre (operation 1), and 89 g/litre (operation 2), measured intraoperatively before infusing the Cell Saver®5 infusate. Figure 1 shows the Hb levels from the preoperative day through to discharge for both procedures. Aside from a 37% prolongation of prothrombin time and 27% prolongation of activated partial thromboplastin time on the first postoperative night, coagulation rapidly returned to normal values. The patient recovered uneventfully and despite persistent anaemia (Figure 1), was discharged home after 1 week on both occasions. Two-year follow-up confirms successful revision arthroplasties.

Conscious Sedation and Analgesia for Routine Aortofemoral Arteriography: A Prospective Evaluation

To compare the effectiveness of temazepam and midazolam hydrochloride with or without fentanyl citrate versus a placebo in promoting patient acceptance of diagnostic aortofemoral arteriography. One hundred twenty-five patients undergoing aortofemoral arteriography were prospectively and randomly assigned to one of four treatment arms: placebo (group A), oral temazepam (group B), intravenous midazolam (group C), or intravenous midazolam and fentanyl (group D). Patients were blinded to the administered sedative. Five-point scales were used to assess degree of patient discomfort, willingness to undergo the same procedure again, patient compliance, and preprocedural anxiety. There was no difference between patient groups in willingness to return for a repeat procedure (P: =.89). Group C patients were less compliant during the procedure (P: =.034). Mean patient discomfort scores were 1.81 for group A, 1.84 for group B, 1. 53 for group C, and 1.27 for group D. Discomfort experienced during the procedure was not related to the degree of preprocedural anxiety (P: =.42). Patients who had previously undergone arteriography reported a higher level of pain than did those who had not (P: =. 021). Most patients experienced only low-level discomfort during diagnostic aortofemoral arteriography. In the authors' opinion, conscious sedation should only be used selectively, not routinely, for diagnostic aortofemoral arteriography.

Pharmacodynamics of temazepam in primary insomnia: assessment of the value of quantitative electroencephalography and saccadic eye movements in predicting improvement of sleep.

Quantitative electroencephalographic parameters and saccadic eye movements are frequently used as pharmacodynamic measures of benzodiazepine effect. We investigated the relationship between these measures and the hypnotic effect. The correlation between the pharmacodynamic measures and sleep quality was determined in 21 patients with primary insomnia. The pharmacokinetic-pharmacodynamic relationships were characterized after administration of 20 mg oral temazepam. The hypnotic effect was determined on the basis of polysomnographic sleep recordings and a subjective sleep evaluation questionnaire. Correlations between pharmacodynamic measures and the improvement of sleep were investigated. The pharmacokinetic-pharmacodynamic relationships for the parameters derived from electroencephalography and saccadic eye movements showed considerable interindividual variability. Administration of temazepam led to a significant improvement in the objective parameters sleep period efficiency, wake time after sleep onset, and sleep efficiency and in the subjective assessment of sleep quality. No significant correlations were observed between the pharmacokinetic-pharmacodynamic-derived parameters and the improvement in objective or subjective sleep parameters. In subjects with primary insomnia the administration of 20 mg oral temazepam results in changes in both the pharmacodynamic measures and in quality of sleep. No individual correlations between the pharmacodynamic measures and quality of sleep were observed. We concluded that the investigated pharmacodynamic measures are of value in the first assessment of clinical efficacy and for the selection of the dose(s) to be investigated in subsequent trials that aim at showing clinical efficacy. However, the conclusive quantification of clinical efficacy should be performed only on the basis of the clinical end point itself.

Benzodiazepines attenuate the pituitary‐adrenal responses to corticotrophin‐releasing hormone in healthy volunteers, but not in patients with Cushing's syndrome

The corticotrophin-releasing hormone (CRH) stimulation test has become established as a powerful tool in differentiating the source of ACTH in patients with Cushing's syndrome. Psychiatric symptoms are common in patients with Cushing's syndrome, and many patients with psychiatric illnesses may show disturbances of function of the pituitary-adrenal axis; both of these groups of patients may be receiving benzodiazepine drugs when presenting for evaluation of their possible endocrine problems. Both animal and human studies suggest that interactions occur between benzodiazepines and the hypothalamo-pituitary-adrenal axis. We have therefore evaluated the effects of a benzodiazepine drug on the pituitary-adrenal response to CRH. We have investigated the effects of 20 mg oral temazepam or placebo on serum cortisol and plasma ACTH after the administration of 100 micrograms i.v. human CRH in 12 healthy volunteers and in 9 patients with Cushing's syndrome. Temazepam significantly inhibited the peak serum/plasma levels and area under the curve for circulating cortisol and ACTH in normal subjects after CRH, but there was no such difference after temazepam in patients with Cushing's syndrome. Our results have shown that temazepam inhibits the pituitary-adrenal responses to human CRH in normal subjects, but not in those with Cushing's syndrome. We believe that inhibition of endogenous AVP by temazepam is the most likely explanation for our findings in healthy volunteers: the hypercortisolaemia in Cushing's syndrome suppresses the release of both endogenous CRH and AVP in portal blood which then results in abolition of the temazepam induced reduction in the pituitary-adrenal response to exogenous CRH, as seen in our patients. These effects of benzodiazepines should clearly be taken into account in patients using these compounds while undergoing endocrine assessment.

Hemodynamic effects during induction, laryngoscopy, and intubation with eltanolone (5β-pregnanolone) or propofol. A study in ASA I and II patients

Study Objective: To evaluate the cardiovascular changes following induction of anesthesia, laryngoscopy, and intubation in patients receiving a bolus dose of either eltanolone or propofol. Design: Randomized, controlled, blind, prospective clinical study. Setting: General operating theaters of a university hospital. Patients: 40 ASA status I and II patients scheduled for elective surgery. Interventions: Patients were premedicated with oral temazepam 20 mg. Anesthesia was induced with either eltanolone 0.58 mg/kg or propofol 1.7 mg/kg, neuromuscular blockade was achieved with vecuronium 0.1 mg/kg, and anesthesia was maintained with enflurane 0.5% to 1.0% in nitrous oxide (67%). Measurements and Main Results: Blood pressure was measured using an automatic oscillometric technique, heart rate (HR) was derived from the ECG, oxygen saturation was measured by pulse oximetry, and cardiac output (Q) was measured by a thoracic bioimpedance technique. Induction of anesthesia with either drug, eltanolone or propofol, decreased arterial systolic (SAP) and diastolic (DAP) blood pressures, Q, and stroke volume (SV). HR increased. Systemic vascular resistance (SVR) was unaltered. After laryngoscopy and intubation, SAP and DAP increased secondary to an increase in SVR. HR also increased; SV decreased in patients receiving eltanolone. Side effects (e.g., apnea occurring for more than 30 seconds, involuntary movements, limb hypertonus) occurred at a similar incidence with both treatments, but pain following injection was greater with propofol (59% vs. 9%). Conclusions: Patients receiving either eltanolone or propofol showed similar cardiovascular changes to induction of anesthesia, although there were greater increases in arterial pressure and HR in those patients receiving eltanolone.

Sedation for Day Care Cataract Surgery

OBJECTIVE: To establish the advantages and disadvantages of three sedation techniques for day care cataract surgery. DESIGN: Randomized allocation of patients into three groups comprising: no sedation, oral temazepam or intravenous fentanyl and droperidol. Assessment of patient anxiety, operating conditions and postoperative recovery by linear analogue anxiety scale, questionnaire and reaction time testing. Surgeons were unaware of the nature of the sedation given. SETTING: Day care cataract ophthalmic surgical unit. PATIENTS: Patients undergoing local anaesthetic day care cataract surgery at Leicester Royal Infirmary. RESULTS: Patients given intravenous fentanyl and droperidol were the least restless during surgery but this was associated with more postoperative problems and a longer hospital stay. Oral temazepam was associated with an increased pain score during the operation. Patients having temazepam were the most restless during surgery. CONCLUSION: No sedation provides operating conditions at least as good as oral temazepam and because postoperative problems are avoided, no sedation may be the best technique for day care local anaesthetic cataract surgery.

The relationship between the concentration of temazepam in cerebrospinal fluid and sedation in man.

Twenty-six patients received oral temazepam and subsequently spinal anaesthesia. Blood and lumbar cerebrospinal fluid temazepam levels were measured together with the degree of sedation. The plasma and cerebrospinal fluid concentrations correlated well with the temazepam dose but even better with the weight standardised dose (r = 0.65, p = 0.0003 and r = 0.75, p = 0.00001 respectively). Both the plasma and cerebrospinal fluid concentrations of temazepam were correlated with the patient's sedation (r = 0.42 p = 0.037, and r = 0.46 p = 0.021 respectively), but neither was strong. Thus, although the drug concentration at the receptor may be a major factor in producing sedation, other factors, possibly the receptor population or their responsiveness, are also important contributors.

Temazepam or midazolam for night sedation. A double‐blind study

The effects of oral temazepam (20 mg), oral midazolam (15 mg) and a placebo were compared for night sedation on the evening prior to surgery in a double-blind study. Patients in the placebo group had significantly worse sleep than those in the temazepam (p = 0.004) or midazolam groups (p = 0.04). There was no significant difference between the two drug groups, nor between the residual effects of the three treatments. Temazepam appears to be somewhat more effective than the ultrashort-acting midazolam in pre-operative transient insomnia.

BENZODIAZEPINE PREMEDICATION IN MINOR DAY-CASE SURGERY: COMPARISON OF ORAL MIDAZOLAM AND TEMAZEPAM WITH PLACEBO

Ninety day-case or short stay patients were allocated to three groups in a double-blind study. The groups received oral midazolam 15 mg, oral temazepam 20 mg or placebo approximately 1 h before surgery. Midazolam was superior to temazepam regarding anxiolysis, sedation and amnesia, but temazepam was superior to placebo. However, delay in immediate and late recovery occurred significantly more often in the patients receiving midazolam than in those receiving temazepam or placebo.

A double-blind controlled study comparing temazepam with papaveretum as premedication for fibreoptic bronchoscopy

One hundred patients undergoing routine fibreoptic bronchoscopy were randomly allocated to receive premedication with either intramuscular papaveretum or oral temazepam in a double-blind manner. They all received atropine before and oxygen during the procedure. Patients found the drugs equally acceptable in terms of discomfort, anxiety and the possibility of repeat bronchoscopy, but more had recall of the procedure with papaveretum. There was no difference in secretions, coughing, relaxation and consciousness, as assessed by the bronchoscopist, but patients who had received papaveretum were more cooperative. Arterial blood gases were performed before and 45 minutes after bronchoscopy. Those given papaveretum had a significant fall in mean arterial oxygen tension of 0.96 kPa, while there was no significant change in the temazepam group. There was also a small mean rise in arterial carbon dioxide tension in both groups, with the mean rise in the papaveretum group (0.625 kPa) being significantly higher than the temazepam group (0.2 kPa). Premedication with temazepam is a useful alternative to papaveretum and has the advantage of oral administration and causing less respiratory depression.

A double-blind controlled study comparing temazepam with papaveretum as premedication for fibreoptic bronchoscopy

One hundred patients undergoing routine fibreoptic bronchoscopy were randomly allocated to receive premedication with either intramuscular papaveretum or oral temazepam in a double-blind manner. They all received atropine before and oxygen during the procedure. Patients found the drugs equally acceptable in terms of discomfort, anxiety and the possibility of repeat bronchoscopy, but more had recall of the procedure with papaveretum. There was no difference in secretions, coughing, relaxation and consciousness, as assessed by the bronchoscopist, but patients who had received papaveretum were more cooperative. Arterial blood gases were performed before and 45 minutes after bronchoscopy. Those given papaveretum had a significant fall in mean arterial oxygen tension of 0.96 kPa, while there was no significant change in the temazepam group. There was also a small mean rise in arterial carbon dioxide tension in both groups, with the mean rise in the papaveretum group (0.625 kPa) being significantly higher than the temazepam group (0.2 kPa). Premedication with temazepam is a useful alternative to papaveretum and has the advantage of oral administration and causing less respiratory depression.

SEDATION FOR UPPER GASTRO-INTESTINAL ENDOSCOPY: A comparison of oral temazepam and i.v. diazepam

Temazepam 20 mg orally was compared with titrated doses of i.v. diazepam as sedation for elective upper gastro-intestinal endoscopy. The mean time from taking oral temazepam to endoscopy was 66 min, and from i.v. diazepam to endoscopy was 10 min. The endoscopists found that the sedation achieved was the same in both groups and allowed adequate examination of the upper alimentary tract. The oral presentation, avoiding the pain of injection and the possible shorter duration of action, made oral temazepam preferable to i.v. diazepam.