A comparison of nitrous oxide and midazolam on cognition and mood

Key Points

• The ability of patients to perform skilled tasks is impaired with midazolam sedation, but not with nitrous oxide/oxygen sedation.

• Midazolam sedation produces enduring amnesia in the peri-operative period but nitrous oxide does not impair memory.

• Patients undergoing midazolam sedation should receive written post-operative instructions, which must prohibit them from undertaking skilled tasks until the drug has been completely eliminated from their body.

• Patients receiving nitrous oxide/oxygen sedation may resume their normal daily activities upon discharge.

Abstract

Objectives

To compare the effects of nitrous oxide and midazolam on cognition and mood.

Design

A three-way, counterbalanced, cross-over study, using patients receiving conscious sedation for routine dental treatment.

Methods

On each of three separate visits, patients performed a computerised test battery to determine baseline cognitive performance. Then, following administration of either midazolam, nitrous oxide, or no drug, patients re-performed the test battery. Finally, patients completed visual analogue scales assessing their subjective mood state.

Results

Relative to baseline performance, midazolam administration produced significantly slower reaction times compared with nitrous oxide and no-drug conditions. Furthermore, patients receiving midazolam were impaired in accuracy relative to the other conditions on many of the cognitive tasks, particularly those assessing the recall of information. Patient performance in nitrous oxide and control conditions did not significantly differ. These results could not be explained by differences in mood between the conditions, as subjective mood ratings during midazolam or nitrous oxide administration were very similar.

Conclusions

It is important for clinicians to be aware that peri-operative recall of information is reduced in patients who have undergone midazolam sedation. This is an advantage for patients who are anxious, and do not wish to be aware of the operative treatment being performed. However, as the cognitive impairment is enduring, an adult escort and written post-operative instructions should be mandatory for midazolam sedation patients. In contrast, the use of nitrous oxide sedation does not significantly impair higher cognitive tasks and thus patients receiving nitrous oxide sedation can resume normal activities in the post-operative period.

Main

Cognitive properties of sedation agents: comparison of the effects of nitrous oxide and midazolam on memory and mood. J. M. Thompson, N. Neave, M. C. Moss, A. B. Scholey, K. Wesnes and N. M. Girdler Br Dent J 1999; 187: 557–562

Comment

This excellent, randomised controlled clinical trial emanates from the sedation unit at Newcastle and is another step forwards in our understanding of the clinical effects of sedation. Although using a relatively small group of patients (18 completed all three sessions), the cross-over nature of the trial meant that statistical differences could he demonstrated in a number of the factors being examined. These were most notable in the midazolam group where cognition (the act of acquiring knowledge through perception, intuition and reasoning) was quite measurably depressed in the intra-operative and post-operative phases.

Although the authors state that there were no significant differences with regard to mood, the data suggest that patients were much calmer in the midazolam group. It would also have been interesting to test a true 'placebo' group (perhaps with the administration of pure oxygen) rather than, or in addition to, a no-drug group. None-the-less, the results demonstrate the changes in cognitive properties brought about by the administration of midazolam.

From a practical viewpoint, there is now sound clinical evidence showing the absolute need for written post-operative instructions following intravenous sedation (and, if applied logically, to oral sedation with the benzodiazepines). Equally, the authors have effectively proved that there is no need for special precautions following nitrous oxide administration. The General Dental Council in its latest advice (Maintaining Standards¹; para 4:16) has already moved some way towards this position and, if evidence based practice is to have any validity, it must be hoped that they will remove the restrictions completely in the next edition.

The constant attention of the Press to accidents and deaths after general anaesthetics for dentistry means that the use of sedation is likely to continue to grow significantly in the coming years. Randomised, controlled clinical trials of this nature are the best way to advance knowledge and to ensure that accidents under sedation do not replace accidents under general anaesthesia.