Adjuvants

Alpha-2-adrenoceptor agonists (clonidine)

Alpha-2-adrenoceptor agonists display numerous different actions in the body. Their inhibition of catecholamine release, in particular norepinephrine (noradrenaline), and synergistic interactions with opioids (and sedatives) are of clinical relevance to analgesia (and sedation) in the ICU. The locus ceruleus has been identified as an essential site of action in the central nervous system. Furthermore, a 2-adrenoceptor agonists interact with the spinal noradrenergic system, resulting in inhibition of nociceptive inputs. Administration of a2-adrenoceptor agonists functionally results in central sympathicolysis. Short-lasting a-mimetic effects can only be observed after bolus administration of a2-adrenoceptor agonists. The only a2-adrenoceptor agonist in clinical use at present is clonidine.

Clonidine was initially introduced into the management of critically ill patients because of its apparent sympathicolytic activity, for example in patients with withdrawal syndrome after chronic alcohol abuse or in patients with tetanus. It has also been shown to be effective in the prophylaxis of delirium tremens and during weaning from long-term mechanical ventilation, which in principle can be considered as iatrogenic withdrawal from opioids and benzodiazepines. Prophylactic dosages range from 0.9 to 1.5 mg/day, but therapeutic dosages must be titrated and guided by cardiovascular variables (heart rate, blood pressure) and may sometimes exceed 15 mg/day. Significant hypotension is a clear sign of (masked) hypovolemia and requires aggressive fluid replacement.

Numerous studies have shown that clonidine acts synergistically with almost all sedatives and analgesics. There is increasing evidence that adjuvant administration of clonidine during long-term mechanical ventilation may facilitate sedation and analgesia, prevent development of tolerance, and simultaneously reduce the dose requirements of sedatives and analgesics. Clonidine dosages usually range from 0.9 to 1.5 mg/day.

Contraindications for clonidine are hypovolemia and severe arrhythmias. Although high clonidine doses may lead to constipation, this effect may be counteracted in most cases because of the reduced dosage requirements of opioids.

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