It has been generally assumed that the bioavailability of different formulations of intravenous diazepam is identical. In a within-subject crossover study using eight healthy volunteers, we have found that both the initial and the overall plasma diazepam levels are significantly lower after both emulsion (Diazemuls) and micelle preparations than after an organic formulation (Valium). These findings are relevant to the interpretation of the results of past, present and future clinical studies involving intravenous diazepam. The studies with Valium and Diazemuls confirm the clinical impression of the lesser potency of the latter formulation.
Emergence excitement or delirium and unpleasant postoperative dreams are the most undesirable sequelae of ketamine. Their occurrence has made it an unacceptable form of anaesthesia in adults, except when there is a specific indication for its use. Psychic sequelae occur more commonly in women than in men' and their incidence is related to the nature and duration of the and of the patient. A number of drugs have been given before, during or after anaesthesia to help reduce undesirable s e q~e I a e ,~* '~~ but it is difficult to compare their efficacy because of the varying types of operations and differing methods of interpretation of data. This paper reports a study in which ten drugs were given, alone or in combination, as intravenous premedication to a standard patient population anaesthet ised with ketamine alone and subjected to a standard follow-up. MethodPatients were undergoing morning minor gynaecological operations in one of two hospital units. The contraindications to the inclusion of a patient in the study were hypertension, a history of a cerebral vascular accident or psychiatric upset.Anaesthesia was induced with 2 mg/kg ketamine and maintained with intermittent doses in the region of 0.25 mg/kg as required. Arterial pressure and heart rate were measured at frequent intervals throughout and observations made during anaesthesia were standardised according to the scheme described by Dundee, Moore & Nich01l.~ Only the incidence of 'unacceptable' anaesthesia is presented here and this is defined as: 'Anaesthetic conditions making surgery difficult or impossible (hypertonus, involuntary movement, etc). or a sustained rise in systolic or diastolic pressure of 30+mmHg, or heart rate above 120 bpm.' These did not preclude the successful completion of the operation as operating conditions were often transformed by the use of nitrous oxide-oxygen with or without halothane or trichloroethylene.Patients were observed closely at the end of operation and the occurrence and severity of emergency delirium noted. This was classed as mild or severe, the latter implying screaming which would upset other patients or attendants. In all instances this was rapidly terminated by the intravenous injection of diazepam, droperidol or physostigmine.At a visit made 6 or 24 h after operation patients were questioned about the occurrence of 'dreams' which were classed as unpleasant or pleasant according to their content. At this visit patients were asked if, in the event of their
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1 Temazepam was administered by aerosol using a standard protocol to healthy volunteers. Two studies are reported in which different dosage formulations were used: a) 30 mg of the 5 ,u diameter particle (n = 6); b) 10 mg of the 2 P, diameter particle (n = 6). 2 An open crossover design was followed in each study. On one occasion in both studies subjects used a gargling procedure to remove drug which had been deposited in the mouth and oropharynx. 3 Serial venous blood samples were drawn for a period of 24 h. The mean total AUC of the 5 ,u preparation was significantly reduced by gargling (3153 ng ml-1 h to 1066 ng ml-' h) (F = 0.32). Gargling also had a significant effect on the mean AUC(0-1 h). 4 In contrast gargling had no significant effect on the mean AUC associated with the smaller diameter particle preparation (630 ng ml-1 h) vs 397 ng ml-1 h (F = 0.74).5 These findings also indicate that temazepam deposition in the pulmonary tree is enhanced by the use of a 2 ,u rather than a 5 ,u diameter particle. However, the plasma drug concentrations achieved are unlikely to produce a sufficiently marked sedative effect for endoscopic investigations such as gastroscopy.
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