Plasma concentrations and pharmacokinetics of bupivacaine with and without adrenaline following caudal anaesthesia in infants.

BACKGROUND: The aim of this study was to determine whether the use of adrenaline 1/400000 added to 0.25% bupivacaine significantly delays the systemic absorption of the drug from the caudal epidural space in young infants. METHODS: Fifteen infants less than 5 months of age undergoing minor lower abdominal procedures under a standardised general anaesthetic were randomised to receive a caudal block with either 0.25% plain bupivacaine 2.5 mg/kg (n=7) or bupivacaine 0.25% with 1/400000 adrenaline (n=8). Blood samples were drawn at 30, 60, 90, 180, 240 and 360 min according to the infant's weight and analysed for total and free bupivacaine concentrations using a gas chromatography-mass spectrometry (GC-MS) technique. RESULTS: The total C(MAX) and T(MAX) were comparable in both groups. The total bupivacaine concentration at t=360 min was significantly higher in the "adrenaline" group compared to the "plain" group, i.e. a median (range) 742 ng/ml (372-1423 ng/ml) vs. 400.5 ng/ml (114-446 ng/ml), P=0.0080. The median "apparent" terminal half-life (t1/2) was significantly longer in the "adrenaline" group (363 min; range 238-537 min) compared to the "plain" group (n=6) (165 min; range 104-264 min), P=0.0087. The free bupivacaine concentrations (n=3 in both groups) ranged between 13 ng/ml and 52 ng/ml, corresponding to a percentage of free bupivacaine between 1.3% and 6.7%. CONCLUSION: The addition of 1/400.000 adrenaline prolongs the systemic absorption of caudally administered bupivacaine in infants less than 5 months of age.

Comparison of two standard techniques of general anaesthesia for day-case cataract surgery.

We have assessed general anaesthesia for day-case cataract surgery in 40 patients more than 60 yr of age. The patients were allocated randomly to receive either an infusion of propofol or etomidate-vecuronium-isoflurane anaesthesia. Patients in the propofol group experienced significant reductions in mean arterial pressure (42%) during anaesthesia. In the etomidate-vecuronium-isoflurane group there was a significant increase in both mean arterial pressure (19%) and heart rate (21%) with intubation. During maintenance of anaesthesia in this group, mean arterial pressure and heart rate decreased to 88% and 80% of awake values. Both techniques produced similar reductions in intraocular pressure. Recovery times from cessation of anaesthesia to spontaneous eye opening and ability to give correct date of birth were significantly shorter in the etomidate-isoflurane group. Two hours after surgery there were no significant differences between the groups and cognitive mental function tests were similar to preoperative values. All patients were deemed fit for discharge home 2 h after surgery. We conclude that it is feasible to provide general anaesthesia for day-case cataract surgery. Etomidate-vecuronium-isoflurane anaesthesia appeared to be superior to propofol in this age group as it was associated with less hypotension and a more rapid recovery.

Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein.

Abetalipoproteinemia is an inherited disorder of lipoprotein metabolism. Affected individuals produce virtually no circulating apolipoprotein B-containing lipoproteins (chylomicrons, very low density lipoprotein, low density lipoprotein and lipoprotein (a)). Malabsorption of the antioxidant vitamin E occurs, leading to spinocerebellar and retinal degeneration. Biochemical and genetic studies show that abetalipoproteinemia is not a defect of lipid biosynthesis or of the apolipoprotein B gene. Instead a microsomal triglyceride transfer protein, which exists as a complex with protein disulphide isomerase in the endoplasmic reticulum, has been implicated. We have cloned and sequenced the human cDNA encoding microsomal triglyceride transfer protein. The predicted amino acid sequence shows extensive homology to vitellogenin, the precursor of the lipovitellin complex, which has been shown by X-ray crystallography to contain a large lipid storage cavity. Microsomal triglyceride transfer protein is expressed in ovary, testis and kidney, in addition to liver and small intestine. A homozygous mutation that disrupts splicing has been identified in affected siblings with classical abetalipoproteinemia. These results elucidate a key process in the packaging of apolipoprotein B with lipid, and should increase our understanding of the processes regulating the production of atherogenic lipoproteins.

Brainstem auditory evoked response during propofol anaesthesia in children.

The effect of propofol on the brainstem auditory response was studied in 10 healthy children presenting for elective general surgery. A computer-controlled infusion of propofol was used to induce and maintain anaesthesia. Basal brainstem auditory evoked responses were recorded in the awake child and at different infusion rates of propofol. Significant increases in the latencies of the brainstem waves III and V and the interpeak intervals I-V and III-V were seen and were dose dependent. The changes were small and would not preclude the use of propofol anaesthesia for brainstem auditory evoked response testing in children.

Effect of propofol anesthesia on baroreflex activity in humans.

Previous studies have shown that infusions of propofol, a new intravenous anesthetic, were associated with decreased arterial pressure and slow heart rates. To evaluate the role of baroreflex mechanisms in sustaining these conditions, the effects of two infusion rates of propofol (54 and 108 micrograms.kg-1.min-1) to supplement 66% nitrous oxide in oxygen anesthesia were studied in twelve ASA class I patients having a mean age of 34 years. Baroreflex control of heart rate was studied by perturbing the patients' arterial pressure with phenylephrine or sodium nitroprusside. Valsalva maneuvers were used to assess the response of the systemic arterial system. Steady state anesthesia at both infusion rates was not associated with decreased sensitivity of the baroreflex control of heart rate, but resetting of the reflex occurred to allow lower arterial pressures for a given heart rate than in the awake state. During propofol infusions at either rate, the diastolic pressure overshoot normally associated with the relief of raised airway pressure in the Valsalva maneuver was significantly reduced. It is concluded that propofol/nitrous oxide anesthesia is not associated with impairment of baroreflex sensitivity, but that central sympatholytic and/or vagotonic mechanisms enable low heart rates to be sustained despite decreased arterial pressures.

Clinical assessment of the neonatal Dinamap 847 during anesthesia in neonates and infants.

Direct measurements of systolic, diastolic, and mean arterial blood pressure and electrocardiogram-derived heart rates were compared with indirect arterial blood pressure measurements using the Dinamap 847XT noninvasive monitor. A total of 260 paired comparisons from 16 patients were analyzed. A regression analysis of paired data over a wide range of blood pressure values gave the following results: for heart rate r = 0.97, for systolic arterial pressure r = 0.84, for mean arterial pressure r = 0.73, and for diastolic arterial pressure r = 0.52. The 95% confidence limits for systolic, mean, and diastolic arterial pressure were +/- 16 mm Hg, +/- 18 mm Hg, and +/- 21 mm Hg, respectively. The Dinamap monitor was found to be an accurate trend recorder of heart rate and blood pressure during anesthesia in neonates and small infants.

Aqueous humour turnover and intraocular pressure during menstruation.

Both intraocular pressure and aqueous humour turnover rate were determined at intervals over three months in three females in order to investigate whether a correlation existed between these variables and the menstrual cycle. Not only was there a lack of correlation between intraocular pressure or aqueous humour flow rate and menses but intraocular pressure and aqueous humour flow rate were also not related to each other. If pharmacologically administered doses of progesterone or oestrogen influence intraocular pressure, the present data indicate that the effect is probably mediated through effects on the aqueous outflow pathways.

Eye drops of RU 486-6, a peripheral steroid blocker, lower intraocular pressure in rabbits.

A peripheral corticosteroid blocker RU 486-6, instilled as a 1% suspension at random into one eye of 12 rabbits, produced a consistent fall in intraocular pressure as measured by a hand-held applanation tonometer, when compared with the fellow control eye. This or a similar drug may be applicable for treatment of human open-angle glaucoma, or ocular hypertension, by eliminating that part of ocular tension attributable to the effect on aqueous outflow of the normal and fluctuating level of tissue corticosteroids.

Comparison of ocular hypotensive effects of acetazolamide and atenolol.

The ocular hypotensive effect of single oral doses of (a) atenolol (50 mg), (b) acetazolamide (500 mg), (c) atenolol (50 mg) and acetazolamide (500 mg) in combination, and (d) vehicle (inert tablets) were compared in 8 patients with glaucoma. In this single-dose, double-masked trial the combination was observed as most effective in reducing ocular tension. Both the combination and atenolol performed markedly better than vehicle. That acetazolamide did not reduce ocular tension significantly more than vehicle is probably explained by relatively low initial ocular tensions. There was no evidence of interaction between atenolol and acetazolamide in this study. Acetazolamide probably remains the first-choice oral medication for glaucoma. It is cautiously suggested that beta-blocking drugs may have a future therapeutic role, but longer-term studies on larger numbers will be required to establish this.

Atenolol eye drops in glaucoma: a double-masked, controlled study.

Guttae atenolol 4% (Tenormin), a pure beta1-blocking (i.e., cardioselective) drug, produced a median overall fall of 5-6 mmHg (range 3-2 to 13-2 mmHg) in the first tonometrised eyes of 7 patients with open-angle glaucoma or ocular hypertension and 1 with closed-angle glaucoma (off any treatment for the whole of the day preceding each test day) after allowance for an 'effect' of guttae saline 0-9%, in a double-masked, cross-over trial. By a Wilcoxon matched pairs rank test this was significant at the P less than 0-05 level. The median overall fall of 3-5 mmHg (range 0-8 to 10-8 mmHg) in the second-tonometrised eyes of 7 patients (1 of the 8 contributed only 1 eye) was also significant (P less than 0-05). In 2 patients who had been treated with guttae atenolol 4% daily 3 X for 1 and 2 months there is evidence that, on replacing the atenolol 4% with saline 0-9%, a rise of pressure of around 3 mmHg occurred 2 and 3 and 5 days later, i.e., the drug still retained its effectivity (slightly reduced) after 1 and 2 months.

Atenolol versus propranolol. A comparison of ocular hypotensive effect of an oral dose.

In a controlled double-blind cross-over trial in 10 patients comprising six with open-angle glaucoma, three with closed-angle glaucoma, and one with ocular hypertension, a single oral dose of atenolol (50 mg) was significantly more effective than propranolol (40 mg) in reducing ocular tension.

Ocular hypotensive effect of atenolol (Tenormin, I.C.I.). A new beta-adrenergic blocker.

Atenolol (Tenormin or I.C.I. 66082) is a new beta-adrenergic blocking drug, unique in being cardio-selective and in having no intrinsic sympathomimetic or membrane activity. In a controlled double-blind study, a single 50 mg oral dose produced a significant fall in ocular tension for about 7 hours in five patients with definite or suspected glaucoma. The average maximum fall was 35 per cent of the initial pressure; it occurred at 5 hours after oral ingestion. Accordingly neither intrinsic sympathomimetic nor membrane activity can account for all the ocular hypotensive effect of beta blockers in humans. The practical implications for treatment of glaucoma require longer-term investigations some of which are in progress.