Continuous sedation in the intensive care unit (ICU) is commonly used to control respiratory rate and anxiety and thus promote sleep and optimize care. The sedatives used most often include propofol, midazolam, and lorazepam.1 These medications provide adequate sedation but also can cause oversedation. Oversedation can lead to prolonged duration of mechanical ventilation and longer ICU and hospital stays.2 The 2013 Society of Critical Care Medicine guidelines for Pain, Agitation and Delirium suggest that providers use non-benzodiazepine sedatives (i.e., propofol or dexmedetomidine) due to the fact that they are associated with better outcomes including reduced duration of mechanical ventilation, shorter ICU length of stay, and a lower incidence of delirium.3-5
Dexmedetomidine, a highly selective central alpha-2-adrenergic-receptor agonist, provides cooperative sedation, sympatholysis, and analgesic-sparing effects without inducing respiratory depression.6 Clonidine on the other hand is structurally similar to dexmedtomidine and the enteral formulation of clonidine has excellent bioavailability (75–88% orally and 86–99% sublingual) and low drug acquisition cost, which allows it to be an excellent alternative to dexmedetomidine.7,8 Most available literature assessed clonidine as an ICU sedative utilizing the IV formulation.9,10
The authors of this study sought to evaluate whether the transition from dexmedetomidine to enteral clonidine is a safe, effective and a less expensive strategy to control agitation. The authors conducted a prospective pilot study where data was collected from January to March 2014 and included all patients treated with dexmedetomidine and then transitioned to clonidine for at least 24 hours.11 Patients transitioning to clonidine were chosen if they had a favorable response to dexmedetomidine for 12–24 hours (Sedation-Agitation Scale (SAS) score of 3–4 indicating the absence of excessive agitation or oversedation and the ability to obey simple commands). In addition, patients had to meet the following: hemodynamic stability with a heart rate (HR) ≥50 beats/minute, mean arterial pressure (MAP) ≥ 65 mm Hg or systolic blood pressure (SBP) ≥ 90 mm Hg without vasoactive support and no atrioventricular (AV) conduction defects greater than first-degree block were included. Furthermore, patients should also have a functional and accessible gastrointestinal tract.11
Clonidine was administered in doses of 0.2–0.5 mg every 6 hours (starting with lower clonidine doses [0.2 mg every 6 hrs] with dexmedetomidine doses < 0.7 μg/kg/hr, body mass < 100 kg, or older patients, and higher clonidine doses [0.3 mg or more every 6 hrs] with dexmedetomidine doses of ≥ 0.7 μg/kg/hr, body mass≥ 100 kg, or younger patients). The dexmedetomidine dose was reduced by 25% of baseline within 6 hours of each clonidine dose if no agitation requiring rescue medications occurs. Discontinuation of clonidine was through a dose taper when patients are no longer agitated or requiring pharmacologic interventions to maintain comfort.
A total of 20 patients were evaluated, 13 patients were receiving invasive mechanical ventilation during dexmedetomidine therapy including 8 when clonidine was started. Fifteen patients were successfully transitioned from dexmedetomidine within 48 hours of starting clonidine. The initial and maintenance clonidine regimens were 0.3 mg every 6 hours. A total of 18 patients (90%) clonidine was given orally or through a feeding tube and 2 patients (10%) sublingually. Fentanyl requirements were lower when clonidine was administered as the only alpha-2-adrenergic-receptor agonist as compared to dexmedetomidine alone (387 vs. 891 μg/day, p = 0.03). There was no ...