ANALGOSEDATION IN HUMANS: WHAT TO CHOOSE?

Analgo-sedation implies the use of intravenous drugs for analgesia and sedation in patients undergoing outpatient operations or one-day surgery, in which vital signs (SpO2, NIBP, HR, RR, EtCO2) are steadily supervised (1,2). Sedation and analgesia are different conditions: some patients may only need sedation, others only analgesia or both. Analgo-sedation allows the operator to work in the most favorable conditions, given that the patient becomes collaborative, extremely quiet and compliant with the procedure, even in cases of hours long procedures, all carried in absolute safety. Milestones in analgo-sedation: Between the 1920’s and the mid 1950’s the only drugs used as sedatives and hypnotics were barbiturates (Somnifen®, Pernocton®, Pentothal®, Evipal®, etc.). The use of barbiturates declined in the 1950’s after the development of the benzodiazepine derivatives. In 1959, De Castro and Mundeleer introduced the concept of neuroleptoanalgesia followed by the release of "Innovar®", a 50:1 combination of droperidol and fentanyl, both originally synthesized by Janssen pharmaceuticals, which was followed on the Italian market by “Leptofen®” (Famitalia). The next advance in analgosedation at the end of 70s, was the release of the steroid anesthetic "Althesin®", a surprising combination of the two steroidal compounds, alfaxalone and alfadolone. In spite of its deplorable histamine release, althesin safety profile due to its highest (30/1) therapeutic index among all anesthetic molecules, bestowed to it a long-lasting popularity. The advent of noncumulative anesthetic molecules brought the new concept of TIVA (Total Intravenous Anesthesia) in the field of analgosedation. Most of this unexpected innovation was due to the hypnotic alkylphenol derivative Propofol® and to the opioid agonist remifentanil hydrochloride, both characterized by fast and alternative metabolic pathways. In virtue of their pharmacodynamics and pharmacokinetics peculiarities, propofol and remifentanil, administered by TCI (Target Controlled Infusion), are nowadays the ideal drugs for analgosedation (3). Administered by TCI, such hypnotic/opioid combination warrants extreme precision in dose titration, fast and predictable variations in analgo-sedation depth, reduction of total administered dose, very fast recovery of consciousness and reduction of hospitalization times. Currently, Remimazolam, a new benzodiazepine now in phase III of clinical experimentation, seems to promise further development and enhancement to the current analgo-sedation techniques (4). It is worth to note that parallel advancement in veterinary analgosedation was provided in the same years by parallel anesthetic formulations named pentothal vet®, Innovar vet®, Saffan® (alfaxalone and alfadolone), Rapinovet® (propofol), and by the off label use of most of the formulations of the anesthetic molecules approved for use in humans.