Usage
Dexmedetomidine is primarily prescribed for the short-term sedation of intubated and mechanically ventilated patients in an intensive care unit (ICU) setting. It is also used for procedural sedation in non-intubated patients before and during surgical or other medical procedures. Additionally, it is indicated for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder.
Pharmacologically, dexmedetomidine is classified as a sedative and analgesic with sympatholytic properties. It acts as a selective alpha-2 adrenergic agonist, specifically targeting the alpha-2A receptor subtype.
Alternate Names
Dexmedetomidine hydrochloride is the chemical name. Precedex and Igalmi are common brand names.
How It Works
Pharmacodynamics: Dexmedetomidine’s sedative and analgesic effects primarily stem from its agonist activity at the alpha-2A adrenergic receptors in the central nervous system. Stimulation of these receptors decreases sympathetic tone, leading to reduced release of norepinephrine. This results in decreased arousal, pain signal transmission, and anesthetic requirements. Dexmedetomidine also produces sympatholysis, resulting in decreased heart rate and blood pressure.
Pharmacokinetics: Dexmedetomidine exhibits linear pharmacokinetics. Following intravenous administration, it is rapidly distributed, reaching peak plasma concentrations within approximately one hour. The drug is extensively metabolized in the liver primarily via glucuronidation and cytochrome P450 (CYP) enzymes, specifically CYP2A6, with a lesser contribution from CYP1A2, CYP2D6 and CYP2E1. Elimination occurs mainly through renal excretion of metabolites, with a terminal elimination half-life of about 2 hours.
Mode of Action: Dexmedetomidine binds to pre- and postsynaptic alpha-2A adrenergic receptors in the locus coeruleus of the brain. Presynaptic binding inhibits norepinephrine release, reducing sympathetic outflow. Postsynaptic binding activates inhibitory pathways, causing decreased neuronal firing and promoting sedation.
Elimination: Dexmedetomidine is predominantly eliminated via hepatic metabolism involving glucuronidation and CYP450 enzyme activity. The metabolites are then excreted renally.
Dosage
Standard Dosage
Adults:
- ICU Sedation: Loading dose of 1 mcg/kg IV over 10 minutes (may be omitted or reduced in elderly patients or those with hepatic impairment or being converted from other sedative therapies); Maintenance infusion of 0.2-0.7 mcg/kg/hr IV (titrated to effect, not to exceed 1.4 mcg/kg/hour). Infusion duration typically not to exceed 24 hours in the ICU.
- Procedural Sedation: Loading dose of 1 mcg/kg IV over 10 minutes (may be omitted or reduced in elderly patients or those with hepatic impairment, or for less invasive procedures); Maintenance infusion of 0.2-1 mcg/kg/hr IV (titrated to effect); For awake fiberoptic intubation: 0.7 mcg/kg/hour IV until the endotracheal tube is secured.
- Agitation (Schizophrenia/Bipolar Disorder): Mild to moderate agitation: initial dose 120 mcg sublingual (SL) or buccal (BUC), if needed may give two further doses of 60 mcg separated by at least 2 hrs with max daily dose of 240 mcg. Severe agitation: initial dose 180 mcg SL or BUC, further two doses of 90 mcg as described above to max daily dose of 360 mcg.
Children:
- ICU Sedation: 1.5 mcg/kg/hr IV initially, then titrate to effect within the range of 0.5-1.5 mcg/kg/hr.
- Procedural Sedation: Dosing guidelines similar to ICU sedation, with careful titration based on the child’s weight and clinical response.
Special Cases:
- Elderly Patients: Dose reduction may be necessary due to age-related decline in hepatic function and clearance.
- Patients with Renal Impairment: No dose adjustment is typically required.
- Patients with Hepatic Dysfunction: Dose reduction is recommended.
- Patients with Comorbid Conditions: Careful monitoring and potential dose adjustments are warranted based on the specific comorbidity.
Clinical Use Cases
- Intubation: Loading dose as per procedural sedation guidelines, followed by maintenance infusion until intubation is complete.
- Surgical Procedures: Dosage as described under procedural sedation, titrated to the desired level of sedation.
- Mechanical Ventilation: Dosage according to ICU sedation guidelines.
- Intensive Care Unit (ICU) Use: Dosage as per ICU sedation guidelines. Duration usually limited to 24 hours, but longer durations may be considered with careful monitoring.
- Emergency Situations: No specific emergency dosing guidelines exist. Individualized dosing based on patient condition and clinical judgment.
Dosage Adjustments
Dose reduction is typically considered in patients with hepatic impairment, elderly patients, and those concurrently receiving other sedatives, anesthetics, hypnotics, or opioids.
Side Effects
Common Side Effects:
Hypotension, bradycardia, nausea, dry mouth.
Rare but Serious Side Effects:
Respiratory depression, sinus arrest, atrioventricular block.
Long-Term Effects:
Withdrawal symptoms (e.g., hypertension, tachycardia, agitation) have been observed following prolonged use.
Adverse Drug Reactions (ADR):
Severe hypotension, bradycardia, and respiratory depression require immediate intervention.
Contraindications
- Hypersensitivity to dexmedetomidine.
- Advanced heart block or severe bradycardia in the absence of a pacemaker.
Drug Interactions
- CYP450 Interactions: Inhibitors of CYP2A6, CYP1A2, CYP2D6 and CYP2E1 may increase dexmedetomidine levels. Inducers of these enzymes may decrease levels.
- Other Medications: Concomitant use with other sedatives, anesthetics, opioids, or antihypertensives can potentiate dexmedetomidine’s effects.
Pregnancy and Breastfeeding
- Pregnancy: Dexmedetomidine crosses the placenta. Use only if the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: Dexmedetomidine is excreted in breast milk. Discontinue breastfeeding or the drug, taking into account the importance of the drug to the mother.
Drug Profile Summary
- Mechanism of Action: Alpha-2 adrenergic agonist.
- Side Effects: Hypotension, bradycardia, nausea, dry mouth.
- Contraindications: Hypersensitivity, advanced heart block (without pacemaker).
- Drug Interactions: Other sedatives, anesthetics, opioids, antihypertensives, CYP2A6 inhibitors/inducers.
- Pregnancy & Breastfeeding: Use with caution, potential fetal/neonatal risk.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: Blood pressure, heart rate, respiratory rate, oxygen saturation.
Popular Combinations
Dexmedetomidine is often combined with other sedatives (e.g., propofol, midazolam) and analgesics (e.g., opioids) to achieve balanced anesthesia or sedation in the ICU.
Precautions
- Pre-existing cardiovascular or respiratory conditions require careful monitoring.
- Caution in elderly patients and those with hepatic impairment.
- Avoid abrupt discontinuation after prolonged infusions due to the risk of withdrawal symptoms.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dexmedetomidine?
A: See detailed dosage section above, specific to clinical situation.
Q2: What is the mechanism of action of Dexmedetomidine?
A: Dexmedetomidine is a selective alpha-2 adrenergic agonist.
Q3: What are the common side effects of Dexmedetomidine?
A: Hypotension, bradycardia, nausea, and dry mouth.
Q4: What are the contraindications for using Dexmedetomidine?
A: Hypersensitivity to dexmedetomidine, advanced heart block without pacemaker.
A: Primarily hepatic metabolism via glucuronidation and CYP450 (CYP2A6, CYP1A2, CYP2D6 and CYP2E1) enzymes; metabolites excreted renally.
Q6: Can Dexmedetomidine be used in patients with renal impairment?
A: Yes, generally no dose adjustment is needed.
Q7: Can Dexmedetomidine be used in pregnant or breastfeeding women?
A: Use with caution; weigh the potential benefits against the potential risks to the fetus or neonate. Consult specialist advice.
Q8: Are there any specific monitoring parameters for patients receiving Dexmedetomidine?
A: Continuously monitor blood pressure, heart rate, respiratory rate, and oxygen saturation.
Q9: What should be done if a patient experiences severe bradycardia while receiving Dexmedetomidine?
A: Discontinue the infusion immediately and consider administering atropine or other supportive measures.
