Intravenous anaesthetics

In recent decades, increasing attention has been focused on the intravenous anaesthetic agents. This interest has been stimulated by the discovery and availability of agents with increasingly favourable pharmacokinetic and dynamic properties, coupled with advances in knowledge of pharmacology and advances in computer technology. For most patients and operative procedures, anaesthesia is induced with a bolus or fast infusion of a short-acting drug, most commonly propofol. Increasingly, anaesthesia is thereafter also maintained with an infusion of an agent with favourable kinetics, again usually of propofol, commonly supplemented with boluses or infusions of opioids. Propofol is also commonly used for procedural and intensive care sedation. It has highly favourable pharmacokinetics and pharmacodynamics for these applications as sedative or hypnotic agent—rapid, smooth onset, minimal accumulation, and rapid smooth offset of effect—but is by no means an ideal agent. In some specific situations, such as when its haemodynamic or respiratory effects are detrimental, use of alternative agents such as ketamine and etomidate are warranted. All the currently available agents have adverse effects, some of which are related to the active compound and some of which are related to the vehicle. Efforts are thus being made to develop new formulations, with fewer adverse effects, and to develop newer and better drugs. In the future we are also likely to see increasing use of older agents, but for newer indications (such as the use of ketamine as an antidepressant).

The use of dexmedetomidine in intensive care sedation

The goals and recommendations for ICU (Intensive Care Unit) patients’ sedation and analgesia should be to have adequately sedated patients who are calm and arousal, so that they can guarantee a proper evaluation and an adequate control of pain. This way, it is also possible to perform their neurological evaluation, preserving intellectual faculties and helping them in actively participating to their care. Dexmedetomidine is a selective alpha-2 receptor agonist, member of theraputical cathegory: “other hypnotics and sedatives” (ATC: N05CM18). Dexmedetomidine is recommended for the sedation of adult ICU patients who need a sedation level not deeper than arousal in response to verbal stimulation (corresponding to Richmond Agitation-Sedation Scale 0 to -3). After the EMA approval, some European government authorities have elaborated HTA on dexmedetomidine, based on clinical evidence derived from Prodex and Midex trials. Dexmedetomidine resulted to be as effective as propofol and midazolam in maintaining the target depth of sedation in ICU patients. The mean duration of mechanical ventilation with dexmedetomidine was numerically shorter than with propofol and significantly shorter than with midazolam. The resulting favourable economic profile of dexmedetomidine supported the clinical use in ICU. Dexmedetomidine seems to provide clinical benefits due to the reduction of mechanical ventilation and ventilator weaning duration. Within the present review, an economic analysis of costs associated to the use of dexmedetomidine was therefore performed also in the Italian care setting. Thus, four different analyses were carried out based on the quantification of the total number of days in ICU, the time spent on mechanical ventilation, the weighted average number of days with mechanical ventilation or not and TISS points (Therapeutic Intervention Scoring System). Despite the incremental cost for drug therapy associated with dexmedetomidine, a reduction of the management costs for ICU has been estimated, with savings ranging between € 800 and € 1,400 per patient.