Your new favorite analgesic: using alpha 2's to your advantage
Using Alpha-2’s to your Advantage
Tasha McNerney CVT, CVPP, VTS (Anes.)
1. To understand the function of dexmedetomidine as an analgesic
2. To understand proper patient selection with dexmedetomidine
3. To understand the different routes of administration of dexmedetomidine
Many clinics throughout the world use dexmedetomidine for sedation. But, did you know that dexmedetomidine is also labeled as an analgesic a fact that often gets overlooked in practice. Dexmedetomidine is the active S-enantiomer of the α-2 agonist medetomidine. Removal of the inactive molecule, levomedetomide results in dexmedetomidine being a “purified” product with increased potency and decreased stress on the liver. Many practices are familiar with dexmedetomidine as an alpha-2 agonist sedative that is reliable, fast-acting, and reversible with antipamezole.
Dexmedetomidine and medetomdine’s main effect are to produce sedation with both somatic and visceral analgesia. Analgesic effects of dexmedetomidine are principally due to spinal anti-nociception via binding to non-noradrenergic receptors (heteroreceptors) located on the dorsal horn neurons of the spinal cord. (Stein, 2013) This mechanism of action inhibits the release of norepinephrine (a catecholamine released by the adrenal gland and part of the fight-or-flight response) and therefore prevents transmission of further nerve impulses. This provides both sedation and analgesia.
Dexmedetomidine is also being used frequently as an in hospital constant rate infusion for rough recoveries and breakthrough analgesia. Constant rate infusion of low dose dexmedetomidine (1 to 2 mcg/kg/hr); can be used in severely painful or anxious patients to provide sedation and analgesia. Dexmedetomidine can also be added to a preexisting opioid infusion for increased sedation and analgesia. Because dexmedetomidine has the potential to cause severe bradycardia and hypotension, these patients should be monitored very closely by a dedicated recovery technician. A loading dose of at least 0.5 µg/kg (0.0005 mg/kg) dexmedetomidine IV should precede the initiation of the dexmedetomidine CRI (Zeltman, 2013).
Epidural use of dexmedetomidine can enhance the analgesic effects of other agents given epidurally. Besides the previously mentioned action at heterotropic spinal receptors, dexmedetomidine also produces analgesia by stimulation of cholinergic interneurons when given epidurally (Gaynor & Muir, 2009) It acts synergistically with epidural opioids, improving the quality and duration of analgesia, and recent human studies have shown that the addition of 2 μg/kg dexmedetomidine epidurally to 2.5 ml of intrathecal bupivacaine prolongs the duration of analgesia, and decreases the requirement of rescue analgesics in patients undergoing lower-limb orthopedic surgery (Jain, 2012) It should be noted that, dexmedetomidine is highly lipophilic, and is rapidly absorbed from the epidural space, which can lead to systemic levels of the drug.
Dexmedetomidine is gaining some ground recently as more practices are experimenting with using it transmucosally in felines, in addition to the intra-muscular and intra-venous routes. Transmucosal dosing allows even fractious cats to receive sedation and analgesia. Often cats given transmucosal dexmedetomidine are not at a surgical plane of anesthesia but are sedate enough to allow physical exams, blood draws, and IV catheter placement. Dexmedetomidine can also be combined with buprenorphine and given via the oral-transmucosal route (Santos, 2010). Oral dosing can range from 20-40mcg/kg.
It should be noted that dexmedetomidine has serious cardiac side effects and seriously effects cardiac output. Dexmedetomidine and medetomdine should be reserved for patients that are heart healthy and have no exercise intolerance. Αlpha-2 agonists are not intended for animals with respiratory or cardiovascular compromise.
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Grosu, I. & Lavand, P. (2010) The Use of Dexmedetomdine for Pain Control. F1000 Medical Reports v.2 2010 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026617/
D Jain, RM Khan, D Kumar, N Kumar (2012) Perioperative effect of epidural dexmedetomidine with intrathecal bupivacaine on haemodynamic parameters and quality of analgesia. Southern African Journal of Anaesthesia and Analgesia Vol. 18 (2)
O’Mara, Kelian, et. Al. (2012) Dexmedetomidine vs Standard Therapy with Fentanyl for Sedation in Mechanically Ventilated Premature Neonates. J Pediatric Pharmacology & Therapy Jul-Sep; 17(3): 252-262
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Zeltman, Phil. (2013) CRI’s: Base Drug Choice on Patient Need, Health. Veterinary Practice News, June 2013. Pg 35