Alpha2-adrenoceptor agonists in intensive care medicine: prevention and treatment of withdrawal

Sympathetic hyperactivity reactions in ICU patients have recently gained attention. These reactions include tachycardia, hypertension, agitation, sweating and an elevated plasma norepinephrine level. This symptom complex has been named ‘sympathetic hyperactivity syndrome’. First studies have demonstrated an increased incidence of post-operative complications in ICU patients with sympathetic hyperactivity. These symptoms can be frequently observed in critically ill patients with chronic alcohol or drug abuse, in those undergoing long-term mechanical ventilation or during weaning from mechanical ventilation under a high dosage of opioids or sedatives. We hypothesize that resistance to opioids or sedatives occurs because of a dysregulation or imbalance of the noradrenergic system. Alpha2-adrenoceptor agonists may counteract such dysregulation as a result of an inhibition of central and peripheral norepinephrine release. Several studies in critically ill patients at risk have demonstrated that sympathetic hyperactivity symptoms can be effectively prevented and treated with α2-adrenoceptor agonists such as clonidine. Furthermore, resistance to opioids and benzodiazepines in long-term ventilated patients could be prevented with clonidine. Clonidine also significantly facilitates weaning from mechanical ventilation