Dr. G.K.KUMAR MD.,DA. Asst.Professor Madras Medical college Chennai 1 2 • WOULD YOU LIKE TO SEDATE YOUR PATIENT ? • WOULD YOU EXPECT PATIENT SAFETY? “SAFE ANESTHESIOLOGIST” 3 SAFE ANESTHESIOLOGIST ‘SAFEST DRUG’ 4 SAFEST DRUG? 5 Dexmeditomidine -Clinician ’s journey 6 KEY POINTS • JOURNEY WITH DEXMEDETOMIDINE • ALPHA2 AGONISTS • CLONODINE TO DEXMEDETOMIDINE 7 α2 Agonists •The initiation for the use of α2 agonists in anesthesia resulted from observations made who were receiving clonidine therapy. 8 α2 Agonists -Effects •Sedation • Anxiolysis • Hypnosis • Analgesia • Sympatholysis 9 α2 Agonists α2 Receptors 10 α2 Receptors Alpha2-adrenoceptors are located in • CNS & PNS • Vascular smooth muscle • Other organs-Liver ,Platelets,Kidney,Pancreas 11 α2 Receptors Location • CNS & PNS • Pre & Postsynaptic Action • Produce inhibitory functions 12 Action of Dexmedetomidine CNS SEDATION, SYMPATHOLYSIS SC ANALGESIA PNS ANALGESIA 13 JOURNEY WITH DEXMEDETOMIDINE 14 Dexmedetomidine • Dextro (s) isomer of medetomidine • Introduced 1999 • Approved for short term sedation by FDA –USA 15 Dexmedetomidine • An intravenous anesthetic agent • Selective α2 receptor agonist. (2:1 1620:1) • Provides -Sedation -Anxiolysis -Analgesia • . 16 Dexmedetomidine • No respiratory depression. • Mild antihypertensive effects • Decrease the need for other analgesic medications such as opioids 17 Mechanism of Action of Dexmedetomidine NE release decreased SEDATION, SYMPATHOLYSIS Binding on alpha2 receptor ANALGESIA Inhibit Firing rate & Substance P release ANALGESIA 18 ? Pharmacological profile • • • • 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 19 Difference from other sedatives • Patients sedated, but, arousable, alert, and to respond without uncomfortable • They may quickly return to sedation again 20 Hemodynamic effects of Dexmedetomidine • Reduces sympathetic activityreduction in HR & BP • No rebound effects 21 Respiratory effects of Dexmedetomidine • NO RESPIRATORY DEPRESSION A in Comparison of the Sedative, Hemodynamic, and Respiratory Effects of Dexmedetomidine and Propofol Children Undergoing Magnetic Resonance Imaging Analg-Anesthesia july 2006 22 Special considerations • Hypovolemic patients • With other vasodilators or negative chronotropic agents dexmedetomidine have an additive effect • With renal or hepatic impairment, metabolites may accumulate and dose reductions may be necessary 23 Dexmedetomidine Contraindications • 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 (advanced heart block) • Patients with impaired ventricular functions (ejection fraction <30%). 24 DOSAGE • 2 ml (200µgs) +48 ml NS • Loading dose -0.5µg-1µg/kg over 10 min (36-72 ml /hr) • Maintenance -0.3µg-0.7µg/kg/hr[4-9ml/hr] • Titration ±0.1µg/kg/hr.-1.25ml/hr 25 Administration 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. 26 Uses of Dexmeditomidine • • • • • • • Bariatric surgery Sleep apnea patients Craniotomy: aneurysm, AVM [hypothermia] Cervical spine surgery Off-pump CABG Vascular surgery Thoracic surgery 27 Uses of Dexmeditomidine • • • • • • • Conventional CABG Spine surgery, evoked potentials Head injury Burn Trauma Alcohol withdrawal Awake intubation 28 Clinical Uses of Dexmeditomidine • • • • SEDATIVE SOLE ANAESTHETIC ADJUVANT OTHERS 29 SEDATIVE • • • • • • • • ICU sedation. Procedural sedation -gynecological -urological -burns patients -pediatric patients Sedation during RA OBESE,OSA Patients 30 SEDATIVE • As sole sedative during percutaneous carotid artery stenting in a patient with severe chronic obstructive pulmonary disease • j p cata; e folch minerva anestesiologica date: 2009 nov volume: 75 issn: 1827-1596 publication 31 SEDATIVE FIBROPTIC INTUBATION • Preservation of arousability • Respiratory-sparing properties -safer conduct of AWAKE FIBEROPTIC INTUBATIONS in difficult airway cases. • Vol. 17, no. 1, 2007 international traumacare (ITACCS 32 ENT SURGERIES • Analgesia, adequate sedation and surgical comfort without adverse effects for patients undergoing FESS under LA • European Journal of Anaesthesiology: January 2008 - Volume 25 - Issue 1 - p 22-28 33 MONITORED ANESTHESIA CARE • Effective baseline sedative for a broad range of surgical procedures • Better patient co operation • Less opioid requirements • Less respiratory depression than midazolam and fentanyl • Dr. Keith A. Candiotti, department of anesthesiology, perioperative medicine and pain management, 34 university of miami-Anes-anal may2009 PREMEDICATION • • • • IV 0.3 - 0.6ug/kg 15mins prior surgery IM 2.5ug/kg 45-90mins prior Effective Stress attenuation Reduces thiopentone doses(±30%) *Miller 7 th edition 35 STRESS ATTENUATION • Preoperative a single dose(1µg/kg) result in progressive increases in sedation • Blunt the haemodynamic responses during laryngoscopy • Reduce opioid and anaesthetic requirements • Decrease blood pressure and heart rate as well as the recovery time after the operation Drugs in R& DVolume 7, Number 1, 2006 , pp. 43-52(10) 36 STRESS ATTENUATION • A bolus dose of 1μg/kg over 10 minutes, prior to administration of reversal provided hemodynamic stability associated with extubation • D. Jain, R. Khan & M. Maroof The Internet Journal of Anesthesiology. 2009 Volume 21 Number 1 37 ANALGESIC • • • • Intravenous Adjuvant in SAB/epidural Intra articular IVRA 38 ANALGESIC • The primary site of analgesic action is thought to be the spinal cord • Both supra spinal and spinal, modulate the transmission of nociceptive signals in the CNS • Systemic use of dexmedetomidine shows narcotic sparing • Analgesic property similar to remifentanil 39 AS ADJUVANT • Intraoperative infusion of dexmedetomidine reduces perioperative & post op analgesic requirements • • Dr. Alp Gurbet, Uludag, Department of Anesthesiology and Reanimation, University Faculty of Medicine, GorukleCAN J ANESTH 2006 / 53: 7 / pp 646–652 40 ADJUVANT TO REGIONAL ANAESTHESIA • IV administration- prolongs the sensory and motor blocks of bupivacaine spinal analgesia with good sedation effect and hemodynamic stability • • Mahmoud Al-Mustafa, MD, Department of Anesthesia and Intensive Care, Jordan University Hospital, M.E.J. ANESTH 20 (2), 2009 41 ADJUVANT TO REGIONAL ANAESTHESIA • 5 μg with spinal bupivacaine in surgical procedures produces prolongantion of duration & better quality of spinal analgesia. • American Journal of Applied Sciences 6 (5): 882-887, 2009 42 ADJUVANT TO REGIONAL ANAESTHESIA • Addition of dexmedetomidine to LA in IVRA improve the quality of anaesthesia and decreased analgesic requirement • Enhances local anesthetic action via alpha 2A receptors • European journal of anestheiology(2005), 22 : 447-451 43 AS SOLE ANESTHETIC • • • • Awake Thyroidectomy Awake Craniotomy, Laminectomy Awake Laryngoplasty Surgeries for Tracheomalacia • • • • Militory med jan 2009 Journal of Clinical Anesthesia - Volume 21, Issue 6 (September 2009 Journal of Clinical Anesthesia - Volume 21, Issue 6 (September 2009 Chicago, IL 60612, USASurgical Neurology 63 (2005) 114–117 44 NON ANESTHETIC USES • Opioid/BZD withdrawl • Alcohol withdrawl • Sedative in sleep deprived patients • Antishivering 45 Clonidine Vs Dexmedetomidine Clonidine • • • • • Selectivity: 2:1 200:1 t1/2 8 hrs1 PO,IV,patch,epidural Antihypertensive Analgesic adjunct Dexmedetomidine • Selectivity: 2:1 1620:1 • t1/2 2 hrs • Intravenous • Sedative-analgesic • Primary sedative 46 47 Dr.G.K.Kumar 48 Dr.G.K.Kumar 49 α2 Receptors • Mediates synaptic transmission in pre- and postsynaptic nerve terminals – Decrease release of acetylcholine – Decrease release of norepinephrine • Inhibit norepinephrine system in brain • Inhibition of lipolysis in adipose tissue • Inhibition of insulin release in pancreas • Induction of glucagon release from pancreas • platelet aggregation 50 Ropivacaine 51 HYPE? HOPE? 52 OTHER ALPHA2 AGONISTS INTRODUCED • • • • • • • • GUANABENZ GUANFACINE Α-METHYLDOPA ROMIFIDINE DETOMIDINE XYLAZINE MEDETOMIDINE DEXMEDETOMIDINE 53 • a2-adrenoceptors: are found in both the central and peripheral nervous system. They are found both pre- and postsynaptically and serve to produce inhibitory functions. • -Presynaptic a2 receptors inhibit the release of noradrenaline and thus serve as an important receptor in the negative feedback control of noradrenaline release. • -Postsynaptic a2 receptors are located on liver cells, platelets, and the smooth muscle of 54 • a2-adrenoceptors: are found in both the central and peripheral nervous system. They are found both pre- and postsynaptically and serve to produce inhibitory functions. • -Presynaptic a2 receptors inhibit the release of noradrenaline and thus serve as an important receptor in the negative feedback control of noradrenaline release. • -Postsynaptic a2 receptors are located on liver cells, platelets, and the smooth muscle of 55 α2 Receptors • • • • • A G protein coupled receptor ALPHA 2a,2b,2c Common effects include: Vasodilation of arteries Vasoconstriction of arteries to heart (coronary artery) • Vasoconstriction of veins • Decrease motility of smooth muscle in gastrointestinal tract 56 Mechanism of action of Dexmedetomidine • Activation of postsynaptic alpha2receptors in the CNS inhibits NE release • Decrease blood pressure , heart rate, sedation , anxiolysis 57 Mechanism of action of Dexmedetomidine Analgesia • Dexmedetomidine on alpha2receptors in the spinal cord. • On PNS decrease firing rate of nerve fibres Inhibit substance P & glutamate release 58 59 60