Adverse effects of intravenously administered drugs used in anaesthetic practice.

Adverse effects of intravenous anaesthetic drugs may be divided into local and general effects. The former include venous sequelae ranging from soreness on palpation on the day after the injection to thrombosis of the whole venous system of the arm. Frequency of venous sequelae for water-soluble anaesthetics 5 to 10%; drugs sparingly soluble in water are similar in this regard when solubilised in 'Cremophor EL'. Diazepam or etomidate dissolved in propylene glycol can produce venous reactions in about 25% of patients on the 3rd day and more by the 15th day if given directly into the vein, and are really only acceptable when injected in an infusion. The general adverse effects of anaesthetic agents include excitatory effects, as well as those on the cardiovascular and respiratory systems which are almost unavoidable. Excitatory effects are diminished by suitable premedication, and the cardiovascular and respiratory effects can be minimised by low dosage and slow administration. Cardiovascular effects of the muscle relaxants are also unavoidable with the drugs presently available, but further research should provide drugs with greater selectivity. More troublesome are the hypersensitivity reactions which occur with both the induction agents and the neuromuscular blocking drugs. These range in frequency from about 1 in 30,000 with the barbiturates to about 1 in 1000 with the 'Cremophor'-containing solutions of propanidid and alphaxalone/alphadolone. However, it appears that the barbiturate reactions are more severe and prolonged. The frequency of hypersensitivity reactions following muscle relaxants is difficult to assess because marked flushing is very common following tubocurarine and bronchospasm can frequently be due to passage of an endotracheal tube. In spite of the alarm created by these reactions, provided the patient is treated in the standard manner, the mortality should be low.

Psychomotor and clinical assessment of flumazenil as an antagonist of midazolam.

The benzodiazepine antagonist flumazenil (0.01 mg/kg) has been compared with doxapram (1 mg/kg) and saline for the reversal of anaesthesia with intravenous midazolam, alfentanil, nitrous oxide in oxygen and isoflurane. The completeness of reversal was assessed by means of a four-choice reaction time test, 1 and 3 h following the antagonist. In addition, the level of sedation was graded using a five-point scale. Psychomotor testing showed that 60 min after administration of the antagonist, there were marked increases in reaction times (P less than 0.05) both in the control and doxapram groups, but not in those receiving flumazenil. At 180 min, however, reaction times in all groups had returned to baseline values. In contrast, there was a significant difference in the sedation scores between the saline and flumazenil groups throughout the study period (P less than 0.05). During the 4 h following midazolam, there was no evidence of re-sedation in any of the groups despite the relatively high midazolam dosage.

The influence of dosage and premedication on induction of anesthesia with minaxolone.

Minaxolone, a new steroid induction agent, was administered to unpremedicated patients at three dose levels and at 0.5 mg . kg-1 to patients receiving three different premedicant regimes. The main side effects observed at induction were involuntary muscle movements but hypertonus and tremor were also seen. Respiratory complications consisted mainly of hiccough. Over the range of doses studied only the latter complication appeared to be dose-related. Premedication with diazepam and especially opiate combinations reduced the frequency and severity of excitatory effects and respiratory upset and increased the proportion of acceptable anesthesia. Marked respiratory depression and hypotension of greater than 20 mm Hg were rare even after opiate premedication.

The effect of air fluidised bed therapy on hypermetabolism in intensive care unit patients.

Major trauma is associated with a hypermetabolic (increased resting energy expenditure) and hypercatabolic (negative nitrogen balance) response. Studies have suggested that nursing injured patients at higher temperatures reduces the metabolic response (Ryan & Clague 1990). In this study the energy expenditure and urinary nitrogen excretion of major trauma patients was examined when nursing them on an air-fluidised bed at 32 degrees C using a crossover study design. Patients were randomised into two groups. Group A patients (n = 8) remained on a standard intensive care unit bed at an environmental temperature of 22 degrees C while Group B patients (n = 6) were placed on an air-fluidised bed operating at 32 degrees C. On days 4 and 5 after injury, energy expenditure and urinary nitrogen excretion were measured. On day 6, Group A patients transferred to an air-fluidised bed and Group B patients to a standard bed. On days 7 and 8, energy expenditure and urinary nitrogen excretion were again measured. Within group comparisons of energy expenditure and urinary nitrogen excretion were made for days 3 and 4 (period 1) and days 7 and 8 (period 2). In both groups, mean energy expenditure was significantly increased in the second period irrespective of whether air-fluidised bed therapy preceded or followed a period on a standard bed. We concluded that nursing intensive care patients on an air-fluidised bed at 32 degrees C did not influence energy expenditure or urinary nitrogen.

Histaminoid responses to atracurium, vecuronium and tubocurarine.

Sixty patients scheduled for elective surgery underwent intradermal testing with 0.1 ml of the following solutions diluted in 0.9% saline: vecuronium and tubocurarine (1 in 1,000), atracurium (1 in 1,000 and 1 in 10,000), thiopentone (1 in 100) and also a 0.9% saline control. Thirty minutes later, an area of erythema of greater than 1.5 cm, or a wheal exceeding 1.0 cm in diameter, was recorded as a positive reaction. The patients then randomly received equipotent doses of atracurium, vecuronium or tubocurarine during a standardized anaesthetic induction. Any cutaneous reaction and the percentage fall in systolic pressure three minutes after administration of the relaxant were recorded. In 51 patients plasma IgE levels were measured. The incidence of positive cutaneous reactions to intradermal and intravenous relaxants was significantly different with each agent (p less than 0.01). The percentage fall in systolic pressure after tubocurarine was significantly different relative to the other two agents (p less than 0.01). This was regarded as reflecting potency in releasing histamine and placed the relaxants in the same order: tubocurarine, atracurium and vecuronium. The response to intradermal administration was no guide to the subsequent response after intravenous administration of the three relaxants. IgE levels below 15 IU X ml-1 occurred significantly more often in females and were associated with a significantly higher incidence of cutaneous reactions after intradermal atracurium (1 in 1,000 and 1 in 10,000) (p less than 0.05 and 0.001 respectively) and tubocurarine (1 in 1,000). With these two agents, generalized flushing after intravenous administration was also more common in this group, relative to the normal/high IgE group.