Rise and decline of the barbiturate methitural for intravenous anesthesia: A systematic search and narrative synthesis

Background

Within the history of intravenous anesthesia, barbiturates represent a chapter of considerable importance. Although the reference barbiturate thiopental had several limitations, it dominated the scene of the intravenous anesthesia until the mid-1980s, when propofol was introduced on the market. In the meantime, several barbiturate derivatives were placed on the market and abounded. This work is aimed at evaluating the clinical impact of the barbiturate derivatives methitural, analyzing the reasons for its rapid abandonment, in the late 1950s.

Methods

A systematic methodology of the search was associated with a descriptive analysis of the bibliography found. A computer-operated search strategy using Medline and Google Scholar databases was implemented. The algorithm was composed by using the words “Diogenal” OR “Thiogenal” OR “Methitural” OR “Metigenal” OR “Neraval” including biochemical and marketed terms. A manual search of the sources was carried out, and precise inclusion and exclusion criteria were established. The narrative synthesis was conducted taken into account the historical context of anesthesia.

Results

The database search yielded 3645 records. Nineteen records were identified through other sources. After duplicates removing (n = 238), and exclusion of not pertinent 3027 records, 314 full-text articles were assessed for eligibility. Of those, other 225 papers were excluded and 89 articles were included in the qualitative synthesis.

Conclusion

Although methitural could be useful in particular surgical settings such as short-acting surgery, and in patients with liver diseases, a limited advantage over thiopental, and its scarce market diffusion due to increased costs, have limited its use. Through a critical analysis of literature, the lack of high-quality studies does not allow us to draw definitive conclusions on the drug.