The drug has also been used successfully in a few other off-label indications. Similar to midazolam, ketamine, and triclofos, dexmedetomidine has been used as an oral premedication at doses of 2–4 µg/kg in pediatric patients. Faritus et al. [2] used dexmedetomidine premedication at a dose of 2 µg/kg in pediatric patients aged 2–12 years scheduled for congenital heart disease surgery and found dexmedetomidine superior to oral midazolam premedication. When dexmedetomidine is administered orally, there is extensive first-pass metabolism with oral bioavailability of around 16%. Therefore, a higher dose is required when it is used for oral premedication [3].

Intra-articular infiltration using a cocktail of agents has been explored for arthroplasty and arthroscopic surgery. Drugs like local anesthetics (lidocaine, bupivacaine, and ropivacaine), clonidine, opioids (morphine and fentanyl), ketorolac, and magnesium have been used in various combinations and at different concentrations for intra-articular infiltration. Alipour et al. [4] randomized 46 patients scheduled for arthroscopic knee surgery and used 1 µg/kg of dexmedetomidine infiltration (in a volume of 25 ml) in one group and placebo (normal saline) in the other group. The 23 patients who received dexmedetomidine infiltration were more comfortable, with significantly less opioid consumption postoperatively.

Alpha₂ agonists inhibit the release of norepinephrine at peripherally located nociceptors by acting on alpha2 adrenergic presynaptic receptors. Dexmedetomidine could exert some effect due to systemic absorption, but the dose when used as an adjunct in infiltration is the same as the intravenous loading dose. The recommended dose used intra-articularly, subcutaneously, and for infiltration is the same as that used for a loading dose. The systemic absorption is definitely slower than when given intravenously.

Lidocaine with adrenaline skin infiltration is a standard practice in many surgeries, especially orthopedic, head and neck, and neurosurgery, and reduces the blood loss via vasoconstriction caused by adrenaline. Postoperative bupivacaine/ropivacaine skin infiltration is practiced at several centers. The addition of dexmedetomidine to lidocaine with adrenaline for skin infiltration has not been explored in detail. Skin infiltration with 1 µg/kg of dexmedetomidine has been shown to improve postoperative analgesia. Mandal et al. [5] used 1 µg/kg of dexmedetomidine with lidocaine and adrenaline infiltration for maxillofacial surgery preoperatively after inducing anesthesia and found that there was less surgical bleeding, reduced anesthetic and opioid requirements, stable hemodynamics, and early discharge from the postanesthesia care unit when compared with lidocaine and adrenaline plus placebo (normal saline). Bradycardia and drowsiness are problems encountered after subcutaneous use and when used in infiltration.

Although dexmedetomidine appears to be effective in several off-label indications, adequately powered studies and subsequent meta-analyses are required before considering dexmedetomidine as a cost-effective modality for the above-mentioned situations.