Dexmedetomidine and Clonidine

Abstract

In the critical care setting, α-2 agonists present a multifaceted profile: sedation combined with arousability, suppression of delirium, preservation of respiratory drive, reduced O(2) consumption, preserved renal function, and reduced protein metabolism. In addition, this review details the reduced arterial impedance, improved left ventricular performance, preserved vascular reactivity to exogenous amines, preserved cardiac baroreflex reactivity, preserved vasomotor baroreflex activity combined with a lowered pressure set point: these features may explain the good tolerance observed when α-2 agonists are used as continuous infusion without any loading dose. Reviewing the literature allows one to suggest that a new management appears possible with arousable sedation. However, it remains to be demonstrated whether this arousable sedation can be combined with the preservation of spontaneous ventilation, in the setting of severe respiratory distress, as opposed to conventional controlled mechanical ventilation combined with conventional sedation. Should such a speculative view be confirmed, then α-2 agonists will move from second-line sedative agents to first-line sedative agents. However, key studies are lacking to demonstrate the effect of α-2 agonists on physiological endpoints and outcome. Presently, the existing body of data suggests a niche for the use of α-2 agonists in the critical care setting.

Early severe acute respiratory distress syndrome: What’s going on? Part II: controlled vs. spontaneous ventilation?

“…Borrowing general anaesthesia from the operating room in the CCU, revamped as "analgo-sedation", is inappropriate: the patient needs only indifference both to the CCU environment and to pain (ataraxia and analgognosia i.e. "cooperative sedation") [13,14]. In a setting different from severe ARDS, minimal sedation appears suitable [15].…”

“…If necessary, alpha-2 agonists should be combined with neuroleptics, to −3 < RASS < −2 [13] a) all the optimization of the cardio-ventilatory physiology, delineated in these two chapters, is useless if the respiratory generator is not free of any depressing influence [94] b) conversely, alpha-2 agonists, without optimized cardio-ventilatory physiology, are useless.…”

“…A sedation devoid of circulatory and ventilatory side-effects is the key pharmacological issue: alpha-2 agonists, devoid of respiratory depressant effects [94,121] are to be administered to −3 < RASS < −2 [13]. If high-dose alpha-2 agonists do not generate enough quietness, neuroleptics are to be added: loxapine, haloperidol [13,122,123]).…”

“…A sedation devoid of circulatory and ventilatory side-effects is the key pharmacological issue: alpha-2 agonists, devoid of respiratory depressant effects [94,121] are to be administered to −3 < RASS < −2 [13]. If high-dose alpha-2 agonists do not generate enough quietness, neuroleptics are to be added: loxapine, haloperidol [13,122,123]). Alpha-2 agonists generate no emergence delirium and prolonged elimination, and alter the hypothalamic set-point [124] thus causing slight hypothermia (≈ 35,5°C) [108,109,125] and lower VO 2 during weaning [82].…”

“…Alpha-2 agonists generate no emergence delirium and prolonged elimination, and alter the hypothalamic set-point [124] thus causing slight hypothermia (≈ 35,5°C) [108,109,125] and lower VO 2 during weaning [82]. Thus, "cooperative" sedation [13,126], or little/no sedation [15,127] in non-combative patients, are to be considered [27,30,71]. Then, new ventilator modes (PS, APRV, etc.)…”