Comparison of arterialized venous with arterial blood propofol concentrations during sub-anaesthetic infusions in volunteers.

We have compared propofol concentrations in arterial and arterialized venous blood (from the radial artery at the wrist and a vein in the opposite forearm) in five volunteers during a sub-anaesthetic increasing infusion regimen designed to produce pseudo-steady-state arterial concentrations of 0.06, 0.17 and 0.43 micrograms ml-1. As in a previous study, we found no statistically significant difference between sampling sites (P = 0.66). However, changes in the method of arterialization yielded a reduction in the observed variability, with the arterialized venous propofol concentration lying within +/- 23% (95% reference interval) of the corresponding arterial concentration compared with 1 +/- 43%, as reported previously.

Gastrointestinal effects of sorbitol as an additive in liquid medications.

Certain sugar alcohols, notably sorbitol, are widely used as a vehicle for drugs in liquid oral dosage forms. Gastrointestinal side effects due to osmotically active excipients have been described, but remain an underappreciated cause of diarrhea. Quantitating amounts of sorbitol is difficult due to a lack of compendial listings of such information. A computer search of Physicians' Desk Reference monographs was conducted to identify products that listed or potentially contained sorbitol as an inert ingredient. Standard form letters and telephone calls were used to collect information on the sorbitol content of products identified. Data were compiled for 142 products, and each value was converted to mg/mL as crystalline sorbitol. Some difficulty occurred obtaining requested information from some manufacturers in their effort to maintain product formulation confidentiality. Pharmaceutical manufacturers should recognize that technically inert ingredients are not necessarily pharmacologically inactive. Manufacturers should therefore comply with requests for, and more openly publish, quantitative information regarding such ingredients, to facilitate the assessment and treatment of patient symptoms.

Effects of intrathecal and intraperitoneal morphine on gastrointestinal motility in the rat.

A method has been developed to compare gastrointestinal (GI) transit time after intrathecal (i.t.) drug injection in the rat. Each animal had a catheter implanted in the i.t. space. Eight rats, on three separate occasions, had either i.t. morphine 16 micrograms kg-1 (in 50 microliters) or intraperitoneal (i.p.) morphine (0.1%) 7.5 mg kg-1 or i.t. saline (50 microliters). The dose of morphine was the ED50 for analgesia by each route. After halothane and oxygen anaesthesia, 10 steel balls and 1 ml of contrast medium were placed into the stomach, the whole procedure being completed within 5 min. Radiographs were taken at 5 min, 3, 6 and 24 h, and the number of balls in the stomach, small and large intestine were counted. The inhibitory effect of i.t. or i.p. morphine on gut motility caused an equally significant delay at 6 h. In a separate series of eight rats the delay by i.t. morphine could be completely antagonized by i.p. naloxone 1 mg kg-1. Thus, i.t. morphine in an analgesic dose even though smaller than the i.p. dose has a similar inhibitory effect on GI tract motility in the rat. This method would enable comparisons on GI transit to be made between a variety of intrathecally administered drugs.

Practice based evaluation of the longterm benefit of second line agents in rheumatoid arthritis.

A hypothetical practice based consortium to evaluate treatment of early rheumatoid arthritis (RA) is discussed. It would consist of a coordinating center and many practicing rheumatologists. Patients with RA within 3 to 12 months of disease onset who met strict entry criteria would be offered enrollment in their choice from a menu of protocols that includes standard and aggressive treatment options and would be followed for a long time. Standard efficacy assessments would be carried out at fairly long intervals, with emphasis on erosive changes in wrist, hands and feet x-rays. Analysis would be done across drug protocols within homogeneous subgroups of patients who have been stratified by comparable entry characteristics, using those who develop erosions during treatment with nonsteroidal antiinflammatory drugs only as the standard for comparison. This approach can be used to identify risk factors that predict subsequent erosive joint damage, and to select a few promising drugs, combinations and therapeutic strategies for subsequent definitive studies.

Investigation of the vasoconstrictor action of subarachnoid haemoglobin in the pig cerebral circulation in vivo.

1. Angiographic techniques have been used to study the influence of intracisternally injected haemoglobin on the diameters of the main intrathecal and representative extrathecal (ascending pharyngeal and facial) cranial arteries of the anaesthetized pig. 2. Intracisternal injection of haemoglobin caused concentration-dependent decreases in the diameters of intra- but not extrathecal arteries suggesting that haemoglobin possesses local vasoconstrictor activity. 3. When infused into one ascending pharyngeal artery, acetylcholine (ACh) caused slight dilatation of the intrathecal arteries but no change in the diameters of the ascending pharyngeal and facial arteries. The dilator response induced by ACh in the intrathecal arteries was converted into frank constriction after intracisternal injection of haemoglobin (cerebrospinal fluid concentration approximately 2 x 10(-5) M). 4. These findings are consistent with the hypothesis that subarachnoid haemoglobin can induce cerebral artery constriction by acting as an extraluminal 'sink' for intimally released endothelium-derived relaxing factor (EDRF) and may be relevant to the pathogenesis of vasospasm after subarachnoid haemorrhage in man.

Delayed recovery from general anaesthesia.

A case of postoperative coma associated with diabetes insipidus and hypothermia is presented. Some recommendations are offered for the future management of similar cases.