What is Dexmedetomidine?
Dexmedetomidine (Dexmed) is a highly selective alpha₂-adrenoreceptor agonist that can provide anxiolysis, sedation, and analgesia.
Alpha₂-adrenoreceptors are found all over the body and reduce the fight-or-flight (sympathetic) response.
Dexmed targets the alpha₂-adrenoreceptors in the brainstem and spinal cord.
In the brainstem, it works on the pons—a crucial hub that helps regulate breathing, sleep, and automatic body functions. It specifically targets alpha₂-adrenoreceptors here, producing sedation that closely resembles natural sleep. This makes it a valuable option in anaesthesia.
It also interacts with alpha₂-adrenoreceptors in the spinal cord, which is thought to contribute to its pain-relieving effects. Interestingly, while we know it’s great at providing analgesia, the exact mechanism behind this remains a bit of a mystery.
What are the advantages of using Dexmedetomidine?
One of Dexmed’s biggest advantages over other agents is its ability to induce sedation by activating natural sleep pathways. By mimicking natural sleep, children maintain their airway tone while sedated and do not experience respiratory depression. This is a massive advantage, as Dexmed can be used safely without causing as much fear of the respiratory drive being affected.
The PROSDEX study was a large, prospective observational study looking at the use of dexmedetomidine for sedation in paediatric intensive care (PICU). It assessed sedation levels using the COMFORT Behaviour Scale (CBS) and found that Dexmed provided effective sedation—both when used on its own and as an adjunct alongside other sedatives.
One of the key benefits of dexmedetomidine is that it is drug-sparing—meaning it reduces the need for other sedatives, helping to minimise their associated side effects. Compared to its sister drug, clonidine, Dexmed is significantly more selective for alpha₂-adrenoreceptors and is linked to fewer side effects.
The PROSDEX study showed that children receiving Dexmed required significantly lower doses of opioids, benzodiazepines, propofol, and ketamine. Additionally, when used alongside regional anaesthesia, Dexmed helps to prolong the analgesic effect, providing longer-lasting pain relief than regional anaesthesia alone.
Beyond its sedative, anxiolytic, and analgesic properties, dexmedetomidine also appears to have organ-protective effects, particularly for the kidneys, heart, and brain.
For example, research suggests that children receiving Dexmed have a lower risk of contrast-induced nephropathy, and in paediatric cardiac surgery, it has demonstrated cardioprotective effects. This is likely because Dexmed helps dampen the sympathetic response to perioperative stress, improving coronary artery perfusion.
Emerging evidence from animal studies also suggests that Dexmed may have neuroprotective properties. While no paediatric studies have confirmed this, the DICE trial (Dexmedetomidine in Infants undergoing Cooling for Neonatal Encephalopathy) is underway. Researchers hypothesise that Dexmed could protect the brain in two key ways: first, through direct neuroprotective mechanisms seen in animal studies, and second, by reducing shivering and providing sedation and analgesia, which may further support brain recovery.
What are the disadvantages of Dexmedetomidine?
The most common side effects of dexmedetomidine are bradycardia, hypertension, and hypotension—all of which are expected given its mechanism of action. Its cardiovascular effects are biphasic, meaning they change over time:
Early phase: When Dexmed is first administered—especially as a loading dose—it can cause hypertension and bradycardia. This happens because it activates alpha₂-adrenoreceptors in vascular smooth muscle, leading to vasoconstriction and a reflex bradycardia.
Later phase: As plasma levels fall, vasoconstriction decreases. Dexmed then reduces sympathetic outflow, which can lead to hypotension.
In most cases, these effects can be managed by reducing the dose or stopping the infusion. However, caution is needed in children who are already on rate or rhythm control medications—such as beta-blockers, digoxin, amiodarone, or calcium channel blockers—as they may be more vulnerable to Dexmed’s cardiac effects.
Extra caution is needed when using dexmedetomidine in neonates, primarily because of their immature liver and blood-brain barrier. Since Dexmed is metabolised by the liver, neonates have reduced drug clearance and increased central nervous system penetration, meaning they may require lower doses to avoid excessive sedation or cardiovascular effects.
Additionally, neonates rely on non-shivering mechanisms, such as vasoconstriction, to regulate their body temperature. Because Dexmed can blunt these responses, they are particularly vulnerable to hypothermia during its use. Careful temperature monitoring and management are essential.
How is Dexmedetomidine administered?
Dexmedetomidine undergoes extensive first-pass metabolism in the liver, rendering it inactive when taken orally. As a result, its oral bioavailability is only about 16%, making oral administration impractical and ineffective.
However, Dexmed is available in multiple other forms, including intravenous (IV), intranasal, intramuscular, buccal, and even nebulised preparations. While it is currently only licensed for IV use, alternative routes have been studied and are widely used in clinical practice.
The intranasal and buccal routes are particularly useful in children, especially those with difficult airways or who are reluctant to take other sedatives. These non-invasive options provide effective sedation while avoiding the need for IV access, making them valuable tools in children’s procedural sedation.
What is the dose of Dexmedetomidine?
Dosing strategies for dexmedetomidine are outlined in the infographic below. As with any sedative, doses should be titrated to effect, keeping in mind Dexmed’s biphasic cardiovascular response:
Loading doses can cause initial hypertension and bradycardia due to vasoconstriction.
Maintenance doses may lead to hypotension as sympathetic outflow is reduced.
Careful monitoring and dose adjustments are essential to optimise sedation while minimising cardiovascular side effects.
Dose adjustments are needed in patients with hepatic impairment, as dexmedetomidine is metabolised by the liver. Reduced liver function can lead to slower drug clearance and prolonged effects so that lower doses may be required.
However, since Dexmed’s metabolites are inactive, no dose adjustment is needed for renal impairment.
How can Dexmedetomidine be used with other agents?
Dexmedetomidine can be used alongside other sedatives and analgesics to enhance clinical outcomes while minimising the adverse effects of those drugs. By reducing the required doses of opioids, benzodiazepines, and other sedatives, Dexmed helps to lower the risk of side effects such as respiratory depression, hypotension, and prolonged sedation. This makes it a valuable adjunct in multimodal sedation and analgesia strategies, particularly in paediatric critical care and procedural sedation.
A study of 17,948 children receiving intranasal sedation found that combining intranasal ketamine and dexmedetomidine (DEX-KET) provided superior sedation compared to either drug alone. One key advantage was that Dexmed helped counteract ketamine’s hypertensive and tachycardic effects, leading to a more stable cardiovascular profile.
Dexmed can also be combined with midazolam (DEX-MID), a pairing that results in more effective procedural sedation than either agent alone. When used intraoperatively, this combination allows for a much lower dose of midazolam while still achieving adequate sedation. However, in both procedural and intraoperative settings, recovery time is prolonged compared to using either drug independently.
When dexmedetomidine is used during general anaesthesia alongside the volatile anaesthetic sevoflurane, it helpsreduce sevoflurane requirements while lowering intraoperative analgesia needs. This can contribute to a more stable anaesthetic course with potentially fewer side effects.
Beyond general anaesthesia, Dexmed is also a helpful adjuvant in regional anaesthesia, particularly when combined with ropivacaine or bupivacaine. This combination leads to a faster onset of action and a prolonged nerve block effect, enhancing pain relief and reducing the need for additional analgesia.
How is Dexmedetomidine used in the ED?
Dexmedetomidine is currently licensed only for adult sedation in an ICU setting, but guidelines exist to support its off-licence use in paediatric intensive care (PICU). Despite this, Dexmed is widely and safely used in PICUs worldwide.
A recent REPEM survey across Europe found that up to 10% of Emergency Departments use Dexmed for procedural sedation in children. However, the latest RCEM Procedural Sedation guideline does not currently list Dexmed as a recommended agent.
In the UK, one example of Dexmed’s use for paediatric procedural sedation in the Emergency Department can be found in Sheffield Children’s Hospital, where their experience and approach are available online.
Future Roles of Dexmedetomidine in the Emergency Department
Dexmedetomidine is increasingly being explored as a paediatric procedural sedation option in the ED. Its sedative properties make it particularly useful for non-painful procedures requiring mild to moderate sedation, such as neuroimaging, where maintaining spontaneous breathing is a key advantage.
For painful procedures, Dexmed could be combined with an analgesic agent (such as ketamine or an opioid) to enhance sedation while allowing for lower doses of both drugs, potentially reducing side effects such as respiratory depression or haemodynamic instability.
One of the most exciting areas for Dexmed in the ED is its availability in non-IV routes. Intranasal and buccal Dexmed are better tolerated than intranasal midazolam and provide effective anxiolysis and sedation, making them a valuable alternative for children who are needle-phobic or distressed.
However, before widespread adoption, a cost-benefit analysis is needed, as Dexmed remains more expensive than many other sedation agents currently used in the ED. Further research and guideline development will be essential to define its optimal role in paediatric emergency medicine.
Take home points
Dexmed provides anxiolysis, sedation, and analgesia.
Dexmed mimics natural sleep and can be used safely without as much fear of the respiratory drive being affected.
Dexmed can be used alone or in combination with other sedative and analgesic medications to reduce the doses and associated side effects.
The most common side effects are bradycardia and a biphasic effect of hypertension initially followed by hypotension.
Dexmed is not widely used in the emergency department but may have future roles in paediatric procedural sedation. The potential to use this intranasally is particularly promising.
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