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Dexmeditomidine Dr.G.K.Kumar What is dexmedetomidine ? • Dexmedetomidine -An intravenous anesthetic agent • Provides -Sedation -Anxiolysis -Analgesia • No respiratory depression. • Mild antihypertensive effects. What is dexmedetomidine ? • Dexmedetomidine - selective α2 adreno receptor agonist. - for sedation in the intensive care unit setting. - decrease the need for other analgesic medications such as opioids What is the mechanism of action of dexmedetomidine? • A selective α2-adrenoceptor agonist. • It’s action is unique and different. • Alpha2-adrenoceptors are located in the CNS, vascular smooth muscle, and a variety of other organs. What is the mechanism of action of dexmedetomidine? • Presynaptic activation of alpha2-adrenoceptors inhibits the release of norepinephrine. • Postsynaptic activation of alpha2-adrenoceptors in the central nervous system inhibits sympathetic activity and can decrease blood pressure and heart rate,so sedation and anxiolysis can result from this activity. • Analgesia is provided through binding of dexmedetomidine to alpha2-adrenoceptors in the spinal cord. What is the mechanism of action of dexmedetomidine? What is the pharmacological profile of dexmedetomidine? • • • • Rapid redistribution: 6 min Elimination half-life: 2 h Protein binding: 94% Metabolism: biotransformation in liver to inactive metabolites + excreted in urine • No accumulation after infusions 12-24 h • Pharmacokinetics similar in young adults + elderly What is the difference between clonidine and dexmedetomidine? Clonidine Dexmedetomidine • Selectivity: 2:1 200:1 • t1/2 8 hrs1 • PO, patch, epidural • Antihypertensive • Analgesic adjunct • Selectivity: 2:1 1620:1 • t1/2 2 hrs • Intravenous • Sedative-analgesic • Primary sedative How does it differ from other sedatives? • This unique sedative quality - someone be clinically sedated yet arousable. • This has not been seen previously with other sedative agents in the intensive care unit. • Patients sedated, remaining so when unstimulated. But, when stimulated, they are arousable, alert, and able to respond without becoming uncomfortable. • It ‘s also observed that they would quickly return to their sleep-like state. In what types of patients dexmedetomidine should not be used? • Infusion over 24 hours. • In obstetric procedures , cesarean section deliveries, as the safety has not been studied. • Patients with pre-existent severe bradycardia and related bradydysrhythmias (e.g., advanced heart block). • Patients with impaired ventricular functions (ejection fraction <30%). • Patients who are hypovolemic or hypotensive. What are hemodynamic effects of dexmedetomidine? • Reduces sympathetic activity, resulting in lower blood pressure and reduced heart rate. • When dexmedetomidine is discontinued, these hemodynamic parameters return to baseline with no rebound effects. What are the respiratory effects of dexmedetomidine? • There is no evidence of respiratory depression associated with the use of dexmedetomidine. Are there any special considerations when using dexmedetomidine? • Prevention of hypotension and bradycardia • Patients who are hypovolemic may become hypotensive - fluid supplementation should be administered prior to and during the administration of dexmedetomidine. • Where other vasodilators or negative chronotropic agents are administered, dexmedetomidine could have an additive pharmacodynamic effect and should be administered with caution and careful titration. How is dexmedetomidine given? • Dexmedetomidine is supplied in a 2-mL ampoule, 100 mcg/ml as the base. • Dexmedetomidine must be diluted in 0.9% sodium chloride to achieve the required concentrations prior to administration. • To prepare the infusion, withdraw 2 ml of dexmedetomidine and add to 48 ml of 0.9% sodium chloride injection to a total of 50 ml. How is dexmedetomidine given? • The target concentration is 4 mcg/ml. So 2 ml of dexmedetomidine needs to be diluted to 50 ml in 0.9% sodium chloride, 4 ml of dexmedetomidine to 100 ml in 0.9% sodium chloride, 6 ml to 150 ml, etc. • Loading dose -0.5µg-1µg/kg [6-12ml]over 10 min • Maintenance -0.3µg-0.7µg/kg/hr[4-9ml/hr] • Titration ±0.1µg/kg/hr. Is dosing affected by renal or hepatic impairment? • Although dexmedetomidine is dosed to effect, metabolites may accumulate with long-term infusions with renal or hepatic impairment, and dose reductions may be necessary. Clinical Uses of Dexmeditomidine • Bariatric surgery • Sleep apnea patients • Craniotomy: aneurysm, AVM [hypothermia] • Cervical spine surgery • Off-pump CABG • Vascular surgery • Thoracic surgery • Conventional CABG • Spine surgery, evoked potentials • Head injury • Burn • Trauma • Alcohol withdrawal • Awake intubation Uses of dexmeditomidine • ICU sedation. • Procedural sedation -gynecological -urological -burns patients -pediatric patients • Sedation during RA • OBESE,OSA Patients Uses of dexmeditomidine • Loading dose 1µg/kg 0.5ml[50µg] diluted as10ml ×10min. • Maintenance 0.3-0.6µg/kg/hr 1.5ml[150µg] diluted in 500ml NS solution conc-0.3µg/ml infusion-16 to32drops/min • Recovery 10-12mins after cessation. What measures were used to determine sedation in clinical studies with dexmedetomidine? • The Ramsay scoring system (Ramsay MA et al: Br Med J 1974:2; 656-659) was used throughout the clinical trials. • It is a 6-point scale as follows: 1 represents anxiety, agitation, or restlessness; 2 denotes cooperative, oriented, and tranquil; • 3 is the patient responds to commands; 4 denotes asleep but with brisk response to light glabellar tap or loud auditory stimulus; • 5 is asleep, sluggish response to light glabellar tap or loud auditory stimulus; and 6 represents deep sedation (asleep, no response)