Effect of Clonidine vs. Dexmedetomidine in Addition to Standard Treatment in Agitated Delirium in Intensive Care Patients: Pilot Study.

Delirium is one of the most common manifestations of cerebral dysfunction in severely ill patients (60 to 80% of ventilated patients), leading not only to short-term complications (prolonged duration of ventilation, prolonged hospital stay, and increased mortality) but also long-term repercussions in the form of impaired cognitive functions, post-traumatic stress syndromes, and decreased quality of life. Different forms of delirium coexist: some patients are very agitated while others are, on the contrary, in an apathetic state. In intensive care patients, the agitated form of delirium is particularly problematic because of the risk of self-extubation and removal of other critical medical devices.

Pain, stress, anxiety and deregulation of wake / sleep cycles are important risk factors for delirium occurrence and are unfortunately frequently encountered in varying degrees in intensive care.

The international guidelines for the prevention of delirium in intensive care recommend the daily application of environmental, behavioral and pharmacological strategies. Thus, the early mobilization of the patient, the respect of the waking / sleep cycles, the adequate control of the pain represent effective measures of prevention. These guidelines also emphasize the importance of minimal use of sedative treatments while ensuring the comfort and safety of patients.

Finally, in the case of the agitated form of delirium, experts recommend the use of low-dose neuroleptics and α-2 agonists to control psychotic manifestations rather than traditional sedatives (mainly benzodiazepines) that can clearly aggravate delirium.

The α-2 receptors constitute a family of receptors coupled to transmembrane G proteins with 3 pharmacological subtypes, α-2A, α-2B and α-2C. The α-2A and α-2C subtypes are mainly found in the central nervous system. Stimulation of these receptor subtypes may be responsible for sedation, analgesia and sympatholytic effects. Α-2B receptors are more common on vascular smooth muscle and have been shown to have vasopressor effects. By their inhibitory action on adenylyl cyclase, the 3 subtypes have several effects: 1) they reduce the levels of cyclic adenosine monophosphate, 2) they cause a hyperpolarization of noradrenergic neurons in the brain stem, in particular in the locus ceruleus, 3) they suppress the neural discharge. This suppression inhibits the release of norepinephrine into the synapse resulting in a modulatory effect on the anxiety, wakefulness and sleep of patients. Activation of this negative feedback loop may also result in reduced heart rate and blood pressure by sympatholytic action.