DexmedetomidineWhy should I make it a Part            of My anaesthetic Practice ?
Dr. Mridul M. Panditrao   CONSULTANT  DEPARTMENT OF ANESTHESIOLOGY AND           INTENSIVE CARE     PUBLIC HOSPITAL AUTHOR...
• FORMERLY:        PROFESSOR & HEAD      In-charge SURGICAL ICU    DEAN OF THE MEDICAL FACULTY     Department of Anaesthes...
For All The Happiness Mankind can gain.  Is not in pleasureBut in rest from “Pain”            JOHN DRYDEN
INTRODUCTION                  Receptors• Classified on the basis of     the actions,  potency and specificity of the neuro...
Adrenergic Receptors• Alpha (α)                        alpha1                                                             ...
Adrenergic Receptors : alpha 2 • pre • post                  & • Extra  synaptic sites of sympathetic terminals     Only t...
Adrenergic Receptors : alpha 2• regulate the release of nor-adrenaline and  adenosine tri phosphate (ATP), through  negati...
Adrenergic Receptors : alpha 2  • Mechanism of action: by modulation of    ion channels causing hyperpolarization of    ce...
alpha 2 Adrenergic Receptor Agonists• Imidazole class of drugs• Older drugs : xylazine                detomidine          ...
alpha 2 Adrenergic Receptor Agonists          Clonidine
Clonidine• first of these drugs for human use• Introduced as a nasal decongestant• ‘side-effects’ : prolonged sedation and...
Parenteral Clonidine• Intravenous: obtundation of pressor  response• As an adjuvant to LAAs :      Neuraxially:         in...
Parenteral Clonidine• Dosages• I.V. : 4 µg/kg for pressor response• Neuraxial:        Spinal:    75 µg in 3 ml Bupivacaine...
alpha 2 Adrenergic Receptor Agonists   Dexmedetomidine    What is so special about it?
Dexmedetomidine• a D – enantiomer of medetomidine• New Entrant in this class• approved in 1999 by FDA for clinical  applic...
Actions• Central    Sedation, anxiolysis and analgesia    Bradycardia and hypotension• Peripheral    Decreased GI secretio...
MECHANISM         CLINICAL CNS EFFECTS• neither the nerve/ terminal is allowed to get  stimulated, nor it can transmit/ pr...
MECHANISM                                CLINICAL CNS EFFECTS     • Spinal: Spinal cord         Binding to 2 receptors an...
CELLULAR MECHANISM Ca++        Ca++         –                       Decrease in action                                    ...
CNS ACTIONS• Sedation – central, G-proteins (inhibition)• Analgesia – spinal cord, Substance P                            ...
CNS ACTIONS• Sedation, resembles the physiologic sleep  with less prominent respiratory depression• Action is supposed to ...
Actions on Cardio-Vascular system• Totally devoid of any direct effects on  myocardium• transient increase in BP : attribu...
PHARMACOKINETICS• Intravenous:  – Distribution t1/2 = 6 minutes  – Elimination t1/2 = 2 hrs  – VDSS – 118 liters – 94% pro...
Biotransformation and Excretion• Through liver with minimal unchanged  fraction• 95% of this metabolized portion is excret...
Clinical Administration• Onset of 30 minutes as compared to that of  midazolam 3-5 minutes and that of propofol  30-50 sec...
Indications & Dosage• A pre-anaesthetic medication and as a  psychosedation in short outpatient surgical  procedures• init...
Indications & Dosage      •     In the dose of 0.2 to 0.7 µg/kg/hr, found to          atenuate the stress induced sympatho...
Indications & Dosage• Can be used to obtund the autonomic  pressor response due to laryngoscopy and  endotracheal intubati...
Indications & Dosage• an intra-operative analgesic in GA as an  alternative to opioids• as a post-operative analgesic• Mor...
Indications & Dosage• It has been found to provide neuro-  protective effect by decreasing cerebral  blood flow without in...
alpha 2 Adrenergic Receptor              Antagonist                Atipamezole• Effectively reverses Psychomotor side-  ef...
To compare the efficacy of   Dexmedetomidine vs Fentanylas sedative & analgesic in short general  anaesthesia in day care ...
AIMS AND OBJECTIVES•To compare the time required for onset and offsetof sedation, quality of intra-operative & post-operat...
METHODOLOGY• Age group 18 - 65 years of ASA-I & II•Randomized into two equal groups of ten each bycomputer generated model...
METHODOLOGY• Induction done with Inj. Propofol 2mg/kg i.v in titrated dose• Maintained with 66% N2O, 33% Oxygen & Isoflura...
RESULTS•   Demographic profile for Age, Sex and ASA grade had no    statistical significance & hence were comparable•   Th...
RESULTS                                                                  Line diagram showing comparision of systolic bloo...
RESULTS                         8                                                                                      Lin...
TO EVALUATE THE EFFECT     OF ADDITION OFDEXMEDETOMIDINE TO 0.5% HYPERBARIC BUPIVACAINE     INTRATHECALLY
AIMS & OBJECTIVES• To study the onset and duration of analgesia with the  addition of 10 µg Dexmedetomidine to 0.5% heavy ...
METHODOLOGY• Patients of ASA I,II and age group 18-65 years were  randomized into two equal groups of 20 each by a  comput...
METHODOLOGY• Sensory block was tested by pinprick method till T6  sensory level• Degree of motor blockade was assessed by ...
RESULTS• No statistically  significant difference  for age, height ,  weight, Sex wise and  ASA distribution in  both groups
RESULTS                                                                                      • Difference in sensory onset...
RESULTSParameters                                 Group A                              Group B                   t     P V...
Multiple bar diagram showing side effect wise distribution of cases in                                                    ...
To compare the Sedation and Analgesia  produced by Dexmedetomidine andButorphanol in Critically Ill patients onMechanical ...
AIMS AND OBJECTIVES•   To compare inj. Dexmedetomidine with inj. Butorphanol as    sole sedative and analgesic in mechanic...
MATERIALS AND METHODS• 20 patients of 20-60 years who needed mechanical ventilation  for post operative or non operative i...
• Vital parameters were recorded at regular intervals• Time interval between the muscle relaxant doses noted• The total re...
RESULTSDemographically there was no significant difference in the 2 groups.                      Bar chart showing compari...
RESULTS                       Haemodynamically patients in both A and B groups were stable                Bar chart showin...
RESULTS                       Line diagram showing comparision of respiratory                                     rate in ...
Indications: Under Trial• Use of dexmedetomidine for post –  operative analgesia given via epidural  route• Use of dexmede...
Indications: Future plans• Use of dexmedetomidine as an  adjuvant to Local Anaesthetic Mixture,  in peri- bulbar block
MULTI MODAL ANALGESIA               (MMA)     The rationale for multimodal analgesia is     achievement of sufficient anal...
“Real World”: Multimodal Analgesia                                                      • Reduced doses    Opioids        ...
Preventive Multimodal Analgesia• Significant improvement in     – Pain reduction     – Opioid use     – Opioid-related AEs...
Multimodal analgesia - methods• Preemptive analgesia• Analgesics  – Single shot  – Infusions  – PCA• Nerve blocks   – Sing...
Multimodal analgesia should consist of….         Combination of Agents• Newer ‘Novel’ Centrally acting I. V. Non-Opioid ag...
Proposed Protocols MMA- I• Pre-medication/ Analgesia with Dexmedetomidine• Dose: 1 µg/ kg I.V. for 10 minutes• Induce with...
Proposed Protocols MMA- II• Neuraxial Blockade with 0.75% ropivacaine;  3 ml intra-thecal or 12-15 ml epidural• Sedation w...
Proposed Protocols MMA- IIIPoint Modifications• Addition of clonidine 1 or 1.5 µg/kg to bupi. In  peri-bulbar/ Supraclavic...
Summarizing• Alpha2 adrenoceptor agonists are very unique  class of drugs• imidazole group• latest entrant: Dexmedetomidin...
Conclusion• Dexmedetomidine is revolutionizing, the intra-  venous anaesthesia• Changing pre-operative sedation, pre-  ana...
Conclusion• In critical care setting as a sedative/ analgesic,  without much deleterious effects, morbidity  and dependenc...
Take Home Message!• Quest for an ‘Ideal’ peri-operative sedative-  analgesic goes on… &… on…&….on!!• α2 agonists are uniqu...
Take Home Message! On the basis of available evidence &            self experience• No Hesitation in making it a part of m...
Dexmedetomidine why should i make it a part of my anaesthetic practice: Prof. mridul M. Panditrao
Dexmedetomidine why should i make it a part of my anaesthetic practice: Prof. mridul M. Panditrao
Dexmedetomidine why should i make it a part of my anaesthetic practice: Prof. mridul M. Panditrao
Dexmedetomidine why should i make it a part of my anaesthetic practice: Prof. mridul M. Panditrao
Dexmedetomidine why should i make it a part of my anaesthetic practice: Prof. mridul M. Panditrao
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Dexmedetomidine why should i make it a part of my anaesthetic practice: Prof. mridul M. Panditrao

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Prof. Mridul M. panditrao gives detailed pharmacodynamics/ kinetics of alpha 2 agonists, centrally action. especially when given via variuos routes, withb help of evidence in the terms of his own conducted trials.

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Dexmedetomidine why should i make it a part of my anaesthetic practice: Prof. mridul M. Panditrao

  1. 1. DexmedetomidineWhy should I make it a Part of My anaesthetic Practice ?
  2. 2. Dr. Mridul M. Panditrao CONSULTANT DEPARTMENT OF ANESTHESIOLOGY AND INTENSIVE CARE PUBLIC HOSPITAL AUTHORITY’S RAND MEMORIAL HOSPITAL GRAND BAHAMA,THE BAHAMAS
  3. 3. • FORMERLY: PROFESSOR & HEAD In-charge SURGICAL ICU DEAN OF THE MEDICAL FACULTY Department of Anaesthesiology & Critical Care D. Y. patil medical college Pimpri, Pune, Inida
  4. 4. For All The Happiness Mankind can gain. Is not in pleasureBut in rest from “Pain” JOHN DRYDEN
  5. 5. INTRODUCTION Receptors• Classified on the basis of the actions, potency and specificity of the neuro transmitters or neuromodulators influencing them• adrenergic receptors : on the basis of effective potency of different naturally occurring or synthetic catecholamines.
  6. 6. Adrenergic Receptors• Alpha (α) alpha1 A alpha2& B beta1• Beta (β) beta2 •Alquist RP. A study of adrenergic receptors. Am j physiol.1948; 153: 586-589 •Langer SZ. Pre Synaptic regulation of catecholamine release. Biochem Pharmacol 1974; 23: 1793-1800
  7. 7. Adrenergic Receptors : alpha 2 • pre • post & • Extra synaptic sites of sympathetic terminals Only the pre-synaptic type of alpha2 receptors are of clinical importanceDrew GM, Whiting SB. Evidence for two distinct types of post synaptic alpha adrenoceptors in vascular smoothmuscle in vivo. Br J Pharmacol. 1979; 67: 207-215
  8. 8. Adrenergic Receptors : alpha 2• regulate the release of nor-adrenaline and adenosine tri phosphate (ATP), through negative feedback mechanism• located in central nervous system, peripheral nerves, vascular smooth muscles, platelets and various splanchnic organs like, liver, kidney, pancreas and eye •Gertler R, Brown H, Mitchell D and Silvius E. Dexmedetomidine: a novel- sedative – analgesic agent. Proc (Baylor Univ med Cent) 2001;14(1): 13-21 www.baylorhealth.com
  9. 9. Adrenergic Receptors : alpha 2 • Mechanism of action: by modulation of ion channels causing hyperpolarization of cell membrane, and suppression of entry of calcium ions at nerve terminals • Suppress, both neuronal firing and release of neurotransmitter, nor- adrenaline • useful mechanisms of action of the drugs which act as alpha2 adrenergic agonists•Cotechhia S. Kobilka BK, et al. Multiple secondary messenger pathways of alpha adrenergic receptor subtypes expressedin eukaryotic cells. J Biochem 1990; 103: 163-224•Birnbaum L. Abramowitz J, Brown AM. Receptor – effector coupling by G- proteins. Biochem Biophys Acta. 1990;1031:163-224
  10. 10. alpha 2 Adrenergic Receptor Agonists• Imidazole class of drugs• Older drugs : xylazine detomidine medetomidine in veterinary medicine! •Clarke KW, Hall LW. “Xylazine” a new sedative for horse and cattle. Vet rec1969; 85: 512-517 •Tamsent A, Gordh T. Epidural clonidine produces analgesia, Lancet1984; 2:231-232
  11. 11. alpha 2 Adrenergic Receptor Agonists Clonidine
  12. 12. Clonidine• first of these drugs for human use• Introduced as a nasal decongestant• ‘side-effects’ : prolonged sedation and severe hypotension.• It was named as ‚Potent centrally acting anti-hypertensive agent‛• Was available only as oral preparation• Parenteral clonidine: Newer applications• Various routes: Intravenous, Neuraxially, regional blocks, peri bulbar etc.
  13. 13. Parenteral Clonidine• Intravenous: obtundation of pressor response• As an adjuvant to LAAs : Neuraxially: intra-thecally as well as epidurally Supraclavicular Block Peribulbar Block
  14. 14. Parenteral Clonidine• Dosages• I.V. : 4 µg/kg for pressor response• Neuraxial: Spinal: 75 µg in 3 ml Bupivacaine Epidural: 75 µg in 10-12 ml LAAs• Supra-clavicular block 1-2 µg/kg• Peri-bulbar block 1-1.5 µg/kg
  15. 15. alpha 2 Adrenergic Receptor Agonists Dexmedetomidine What is so special about it?
  16. 16. Dexmedetomidine• a D – enantiomer of medetomidine• New Entrant in this class• approved in 1999 by FDA for clinical application in humans• Structure:
  17. 17. Actions• Central Sedation, anxiolysis and analgesia Bradycardia and hypotension• Peripheral Decreased GI secretions, inclusive of saliva Decreased GI motility Inhibition of rennin-Angiotensin (RA) system and decreased release of rennin Increased Glomerular Filtration Rate (GFR), Increased excretion of Na, water and thus diuresis Decreased intra-ocular pressure Decreased insulin release
  18. 18. MECHANISM CLINICAL CNS EFFECTS• neither the nerve/ terminal is allowed to get stimulated, nor it can transmit/ propagate the signal forwards.• at supra-spinal level as well as at spinal level Supra-spinal: Locus coeruleus: – Brainstem center - modulates wakefulness – Major site for hypnotic actions (sedation, anxiolysis) – Mediated via various efferent pathways: • Thalamus and subthalamus cortex • Nociceptive transmission via descending spinal tracts • Vasomotor center and reticular formation
  19. 19. MECHANISM CLINICAL CNS EFFECTS • Spinal: Spinal cord  Binding to 2 receptors analgesia At Substantia gelatinosa (Lamina II),  closing the gate at the dorsal horn to stimuli coming from Aδ and C fibers  Inhibit release of nociceptive humoral transmitters like Substance P release of substance P•Kuraishi Y, Hirota N, Sato Y, et al Noradrenergic inhibition of the release of Substance P from the primary afferents in the rabbit spinalcord dorsal horn. Brain res.1985; 309: 177- 182
  20. 20. CELLULAR MECHANISM Ca++ Ca++ – Decrease in action potential due to Ca++ hyperpolarization 2A 2AR Go Gk K+ – + K+ K+ Decrease ininflux of Ca++
  21. 21. CNS ACTIONS• Sedation – central, G-proteins (inhibition)• Analgesia – spinal cord, Substance P Dexmedetomidine
  22. 22. CNS ACTIONS• Sedation, resembles the physiologic sleep with less prominent respiratory depression• Action is supposed to be mediated through α2A subset of receptors and is very specific for dexmedetomidine as compared to clonidine• Are easily arousable and additional sedative/ adjuvant is not needed to maintain the sedation •Hunter JC, Fontana DJ, Hedley LR et al. Assessment of the role of alpha 2 adrenoceptor subtypes in anti nociceptive , sedative and hypothermic action of dexmedetomidine in transgenic mice Br J Pharmacol1997; 122: 1339-1344 •Venn RM, Bradshaw CJ, Spencer R et al. Preliminary UK experience of dexmedetomidine, a novel agent for post operative sedation in intensive care unit. Anaesthesia 199; 54: 1136-1142
  23. 23. Actions on Cardio-Vascular system• Totally devoid of any direct effects on myocardium• transient increase in BP : attributable to peripheral vasoconstriction due to stimulation of α2B adrenoreceptors in peripheral vascular smooth muscles.• significant bradycardia & Hypotension• Secondary to central inhibitory α2A agonist effect• all these effects can be offset or overcome with use of atropine, ephedrine or volume loading
  24. 24. PHARMACOKINETICS• Intravenous: – Distribution t1/2 = 6 minutes – Elimination t1/2 = 2 hrs – VDSS – 118 liters – 94% protein bound• Intramuscular (2µg/kg): – Peak plasma conc 13 18 min (variable) – 70% bioavailability• Enteral: – Buccal - 80% bioavailability – Gastric - 16-20% bioavailability
  25. 25. Biotransformation and Excretion• Through liver with minimal unchanged fraction• 95% of this metabolized portion is excreted through kidney• metabolites do not have any significant pharmacological activity• Thus liver dysfunction may adversely affect the clearance of drug• Impaired renal dysfunction is not known to change the pharmacokinetics of the drug •Gertler R, Brown H, Mitchell D and Silvius E Dexmedetomidine: a novel- sedative – analgesic agent. Proc (Baylor Univ med Cent) 2001;14(1): 13-21 www.baylorhealth.com
  26. 26. Clinical Administration• Onset of 30 minutes as compared to that of midazolam 3-5 minutes and that of propofol 30-50 seconds• can be decreased by infusion of standard loading dose of 1µg/kg, over 10 minutes• Duration of analgesic action of about 4 hours as compared to that of Fentanyl up to 60-80 minutes• Offset of sedative action in 5 minutes, while midazolam has about 2 to 6 hours and propofol has 3-8 minutes.
  27. 27. Indications & Dosage• A pre-anaesthetic medication and as a psychosedation in short outpatient surgical procedures• initial loading dose of intra venous infusion of dexmedetomidine 1- 6 µg / kg for 10 minutes till 3 on Mackenzie’s Sedation assessment score (till the patient showed awakening responses to calling in spite of closed eyes) and maintained on 0.4 µg/kg/hr •Taniyama K, Oda H, Okawa K et al. Psychosedation with dexmedetomidine hydrochloride during minor oral surgery. Anesth Prog 2009; 56:n75-80
  28. 28. Indications & Dosage • In the dose of 0.2 to 0.7 µg/kg/hr, found to atenuate the stress induced sympatho adrenal responses to laryngoscopy, endotracheal intubation, surgical stimulation and provide overall increased hemodynamic stability & as an adjuvant to other anaesthetic agents, including inhalational agents like isofluraneBhatia P. Dexmedetomidine: a New agent in Anaesthesia & Critical care Practice. http://dexmedtomidine.comAanta R, Jaakola ML, Kallio A, Kanto J. Reduction of minimum alveolar concentration of isoflurane by dexmedetomidine.Anesthesiology 1997;80 : 1055-1060
  29. 29. Indications & Dosage• Can be used to obtund the autonomic pressor response due to laryngoscopy and endotracheal intubation• In the dose of 1 µg / kg diluted in 100ml of saline solution, infused over 15 minutes• After a stabilization period of 5 minutes• Suitably induced, relaxed & trachea intubated
  30. 30. Indications & Dosage• an intra-operative analgesic in GA as an alternative to opioids• as a post-operative analgesic• More so used as a sole sedative and analgesic combined in Critically ill patients on Ventilator• Infusion of standard loading dose of 1µg/kg, over 10 minutes followed by maintenance of 0.2- 0.7 µg/kg/hr. diluted in 0.9 % normal salineScheinin B, Lindgren L, Bandel T, Scheinin H, Scheinin M. Dexmedomidine attenuates sympatho adrenal responses totracheal intubation and reduces need for thiopentone and peri-operative fentanyl Br J Anaesth 1992; 68: 126-131Menda F, Koner O, Sayin M, Ture H et al. Dexmedetomidine as an adjunct to anaesthetic induction to attenuatehemodynamic response to endotracheal intubation in patients undergoing fast track CABG. Ann Can J Anaesth 2010’13: 16-21
  31. 31. Indications & Dosage• It has been found to provide neuro- protective effect by decreasing cerebral blood flow without increasing either with cerebral metabolic rate (CMRO2) or intra cranial pressure (ICP)• sole sedating agent with local anesthetic agents in a high risk patient• used as anti-shivering and for thermoregulation•Zornov MH, Maze M, Dyek JB. Shafer SL. Dexmedetomidine decreases cerebral blood flow velocity in humans JCereb Blood Flow Metab 1993; 13: 350-352•Rich JM. Dexmedetomidine as a sole sedating agent with local anesthesia in a high risk patient for axillo-femoralbypass graft: a case report. AANA Journal2005; 73:357-360
  32. 32. alpha 2 Adrenergic Receptor Antagonist Atipamezole• Effectively reverses Psychomotor side- effects• Reverses Sedation & Sympatholysis• Reverses Analgesia• t ½ is 1 ½ - 2 hours.
  33. 33. To compare the efficacy of Dexmedetomidine vs Fentanylas sedative & analgesic in short general anaesthesia in day care obstetric & gynaecological surgeries
  34. 34. AIMS AND OBJECTIVES•To compare the time required for onset and offsetof sedation, quality of intra-operative & post-operative analgesia and the time required for post-operative recovery using Inj. Dexmedetomidineand Inj. Fentanyl• To evaluate cardio-respiratory and any othersystemic side effects at equi-sedative doses
  35. 35. METHODOLOGY• Age group 18 - 65 years of ASA-I & II•Randomized into two equal groups of ten each bycomputer generated model•Pre-medicated with Inj. Glycopyrrolate 0.2mg i.v.• Group A: patients received Inj. Dexmedetomidine 1μg/kg i.v. 10 min. prior to induction by infusion• Group B: patients received Inj. Fentanyl 1μg/kg i.v. 10 min. prior to induction by infusion
  36. 36. METHODOLOGY• Induction done with Inj. Propofol 2mg/kg i.v in titrated dose• Maintained with 66% N2O, 33% Oxygen & Isoflurane ( 0.6 –0.8 %) with the patient breathing spontaneously on Magill circuit• Time to eye opening at the conclusion of surgery was recorded• In post anaesthesia care unit patients were evaluatedperiodically for - vitals - sedation using Ramsay sedation scale - visual analog scale - time of rescue analgesia (when VAS >5) - Standard Aldrete score for post anaesthesia recovery
  37. 37. RESULTS• Demographic profile for Age, Sex and ASA grade had no statistical significance & hence were comparable• The requirement of Propofol was significantly reduced in Dex Group• Comparison of pulse rate in Dexmedetomidine Group showed significant fall immediately after pre medication , without any intervention it returned to baseline, & remained equivalent to that in Fentanyl Group throughout surgery Line diagram showing comparision of pulse rate in study groups• 90 80 P < 0.05 after premedication. 70 60 Average 50 Group A Group B 40 30 20 10 0 On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op PR
  38. 38. RESULTS Line diagram showing comparision of systolic blood pressure in study groups 125 120 115 110 Average No significant change in blood pressure Group A• 105 Group B 100 seen in Dex. group whereas continuous 95 90 On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op fluctuation of systolic BP seen in SBP (mm Hg)fent.group 110 Line diagram showing comparision of SPO2 in study groups 100 90 80• No significant change in diastolic BP & 70 Average 60 Group A 50 Group BRespiratory rate seen in any of the groups 40 30 20 10 0 On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op• significant fall in saturation was observed SPO2 Bar chart showing comparison of eye opening after surgery in studywith Fentanyl group group 7• The time of eye opening is highly 6 5 Group A 4 Averagesignificantly early in Dex. group (p<0.001) Group B 3 2and delayed eye opening seen with 1 0fentanyl group Eye opening after surgery (min)
  39. 39. RESULTS 8 Line diagram showing comparision of VAS score in study groups• The post operative analgesia duration was 6more in Dex. group (approx. 4-6 hrs.), Average Group A 4 Group Bwhereas in Fentanyl group patients required 2rescue analgesia within 1 – 1.5 hrs of surgery 0 At End of surgery At 30 m in At 1 hr At 1.5 hr At 2 hr VAS Score P < 0.001 at 1.5 hrs. Line diagram showing comparision of Ramsay sedation in post operative in study• The sedation was highly significantly groups 4profound in fentanyl group according to 3 Average Group ARamsay sedation score (p < 0.001) after 15 2 Group B 1min of surgery 0 End of surgery At 15 m in At 30 m in At 1 hr At 2 hr Ram say sedation• The quality of recovery was highly P < 0.001 at 15 min. Line diagram showing comparision of standard aldrete score in post operative in study groupssignificantly better (Aldrete score = 9+)was 12 10observed in most of the patients after 30 min 8 Average Group A 6 Group Bin Dex.group & Similar results were seen 4 2only after 1.5 – 2 hrs. in Fentanyl Group 0 End of surgery At 15 m in At 30 m in At 1 hr Standard aldrete score At 1.5 hr At 2 hr P < 0.001 at 15,30, 60 min.
  40. 40. TO EVALUATE THE EFFECT OF ADDITION OFDEXMEDETOMIDINE TO 0.5% HYPERBARIC BUPIVACAINE INTRATHECALLY
  41. 41. AIMS & OBJECTIVES• To study the onset and duration of analgesia with the addition of 10 µg Dexmedetomidine to 0.5% heavy Bupivacaine in sub-arachnoid block• To evaluate the quality of block and post operative analgesia as compared to control i.e. 0.5% heavy Bupivacaine• To observe any side effects of intrathecal administration of Dexmedetomidine with 0.5% Bupivacaine intra operatively and post operatively
  42. 42. METHODOLOGY• Patients of ASA I,II and age group 18-65 years were randomized into two equal groups of 20 each by a computer generated model• Group A (Dexmedetomidine Group) were given 3ml of 0.5% heavy Bupivacaine + 0.5ml (10 µg) of Dexmedetomidine• Group B (Control Group) were given 3ml of 0.5% heavy Bupivacaine + 0.5ml of Water for injection• Patients will be preloaded with Ringer Lactate solution 10 ml/kg body• Spinal anaesthesia was given using a 26G Quincke’s needle in sitting position through a midline approach
  43. 43. METHODOLOGY• Sensory block was tested by pinprick method till T6 sensory level• Degree of motor blockade was assessed by modified Bromage scale• Intraoperative vitals were monitored• Hypotension: SBP < 90 mm Hg or a decrease of >20% from baseline. Hypotension was treated with a bolus administration of 250 ml Ringer lactate and 6 mg of i.v. Mephentermine if required• Bradycardia was defined as HR < 50 bpm and was treated with 0.6 mg of i.v. Atropine• Postoperatively, 2 segment sensory regression, motor regression and time to rescue analgesia were monitored
  44. 44. RESULTS• No statistically significant difference for age, height , weight, Sex wise and ASA distribution in both groups
  45. 45. RESULTS • Difference in sensory onset not statistically significant • Motor onset significantly shorter in Dexmedetomidine Group (t value-2.54, p value < 0.05) Multiple bar diagram showing comparison of time of sensory and motor Peak after spinal anesthesia in study groups • Difference in peak sensory 8 insignificant 7 6 • Peak motor significantly 5Average 4 Group A Group B 3 2 longer in Dex Group(t value- 1 0 4.59, p value<0.0001) Time of Peak sensory (T3) Time of Peak motor(T4) After spinal anesthesia
  46. 46. RESULTSParameters Group A Group B t P Value Mean SD Mean SD Value (n=20) (n=20)2 segment sensory 190.3 34.80 98.65 14.95 10.81 <0.000regression (T5) 1Motor regression 265.05 57.50 138.7 14.76 9.51 <0.000(T6)Time of rescue 342.75 76.94 189 20.71 8.62 1 <0.000 • 2 segment sensoryanalgesia (T7) 1 regression • motor regression Multiple bar diagram showing comparison of level of sensory blockade in study groups 350 300 and 250 • time of rescue 200 analgesia Average 150 Group A significantly longer Group B 100 50 0 in Dex. Group 2 segment sensory Motor regression Time of rescue regression (T5) (T6) analgesia (vas > 7) (T7) Level of sensory blockade
  47. 47. Multiple bar diagram showing side effect wise distribution of cases in study groups 4 • Both groups with 3 manageable No. of cases 2 Group A Bradycardia & Group B 1 0 Bradycardia Side effect Hypotension Hypotension Line diagram showing comparision of systolic blood pressure in study Line diagram showing comparision of diastolic blood pressure in study groups groups 140 90 80 120 70 100 60 80 Average Group A 50 Average Group B Group A 60 Group B 40 40 30 20 20 0 10 op in in in in in in ry op 0 m m m m m m ge t- – 0 5 0 5 0 t3 ur os re t1 t1 t3 t4 t6 Pre – op At 3 min At 10 At 15 At 30 At 45 At 60 End of Post - S A P P A A A A A of min min min min min Surgery op nd E DBP (mm Hg) SBP (mm Hg) Line diagram showing comparision of heart rate in study groups 100 90 80 70 60Average Group A 50 Group B 40 30 20 10 0 op in in in in in in ry op m m m m m m ge t- – 0 5 0 5 0 t3 ur os re t1 t1 t3 t4 t6 S A P P A A A A A of nd E HR (min)
  48. 48. To compare the Sedation and Analgesia produced by Dexmedetomidine andButorphanol in Critically Ill patients onMechanical Ventilation: A Randomized Double Blind Controlled Trial
  49. 49. AIMS AND OBJECTIVES• To compare inj. Dexmedetomidine with inj. Butorphanol as sole sedative and analgesic in mechanically ventilated patients in ICU.• Compare their effects on hemodynamic parameters, autonomic system, post extubation agitation, GCS, nausea, vomiting etc.• Evaluate whether their use reduces the requirement of neuromuscular blocking drug: Vecuroneum.• To compare their cost effectiveness in patients on mechanical ventilation.
  50. 50. MATERIALS AND METHODS• 20 patients of 20-60 years who needed mechanical ventilation for post operative or non operative indication.• As soon as the patient was shifted to the ICU on ventilator (MAQUET SERVO- S ventilator), vital parameters were noted and infusion of the specific drug was started using the syringe pump.• Inj. Dexmedetomidine was started at the rate of 0.7µg/kg/hr and Inj. Butorphanol was started at the rate of 5µg/kg/hr.• Muscle relaxant was given as and when required, while monitoring pulse , blood pressure, peak airway pressure and trigger on the ventilator
  51. 51. • Vital parameters were recorded at regular intervals• Time interval between the muscle relaxant doses noted• The total required dosage of muscle relaxant was calculated after extubation• Patient’s score on Glasgow Coma scale and Brussels sedation score were noted the next day early morning when the muscle relaxants were discontinued and patients were given a trial of weaning• Infusion of the drug was continued until weaning off of the patient from the ventilator or for 24 hours which ever was less
  52. 52. RESULTSDemographically there was no significant difference in the 2 groups. Bar chart showing comparison of average time interval between M.R dose in study group 70 Time interval between 65 60 55 the muscle relaxant doses was nearly 50 45 40 Group A Average Group B double in 35 30 25 20 15 10 Dexmedetomidine 5 0 Average time interval between M.R dose (min) group, hence the Bar chart showing comparison of total requirement of M.R in study requirement of muscle group relaxant was nearly half, 30 suggesting an excellent 25 quality of sedation and 20 Group A analgesia. Average Group B 15 10 5 0 Total requirement of M.R (mg)
  53. 53. RESULTS Haemodynamically patients in both A and B groups were stable Bar chart showing comparison of sedation score in study group 0.8 Patients receiving Butorphanol 0.7 were drowsier as assessed by Brussels’ sedation score but it 0.6 0.5 Group AAverage Group B 0.4 0.3 was not statistically significant; 0.2 0.1 0 Sedation score Bar chart showing comparison of total no of hrs on ventilator in study group Butorphanol group patients needed about 30-60 minutes 18 16 more to be weaned off from the ventilator 14 12 Group AAverage 10 Group B 8 6 4 2 0 Total No of hrs on ventilator (hr)
  54. 54. RESULTS Line diagram showing comparision of respiratory rate in study groups 16 14 Respiratory rate during weaning 12 and after extubation was 10 significantly low in ButorphanolAverage Group A 8 Group B 6 Group, suggesting some amount 4 2 of respiratory depression 0 T0 T1 T2 RR Bar chart showing comparison of Nausea / vomiting in study group Few patients in Butorphanol group complained of nausea and 6 vomiting during weaning and 5 after extubation where as there 4 Group A was no such complaints in patientsNo of cases Group B of Dex. group 3 2 1 0 Nausea / vomiting
  55. 55. Indications: Under Trial• Use of dexmedetomidine for post – operative analgesia given via epidural route• Use of dexmedetomidine as an adjuvant to Local Anaesthetic Mixture given via supra-clavicular Brachial Plexus approach
  56. 56. Indications: Future plans• Use of dexmedetomidine as an adjuvant to Local Anaesthetic Mixture, in peri- bulbar block
  57. 57. MULTI MODAL ANALGESIA (MMA) The rationale for multimodal analgesia is achievement of sufficient analgesia due to additive or synergistic effects between different analgesics, with concomitant reduction of side effects, due to resulting lower doses of analgesics and differences in side-effect profiles.1. Kehlet H et al. Anesth Analg 1993;77:1048-56.
  58. 58. “Real World”: Multimodal Analgesia • Reduced doses Opioids • Improved pain relief • Reduce severity Potentiation of AEs • Earlier dischargeNon opioids :α2 agonistsNSAIDs, coxibs,paracetamol, • Decreased costsnerve blocks Kehlet et al. Anesth Analg. 1993;77:1048-1056 (B).
  59. 59. Preventive Multimodal Analgesia• Significant improvement in – Pain reduction – Opioid use – Opioid-related AEs – Recovery or day ward length of stay – Unplanned admission to the hospitalReuben et al. Acute Pain. 2004;6:87-93.
  60. 60. Multimodal analgesia - methods• Preemptive analgesia• Analgesics – Single shot – Infusions – PCA• Nerve blocks – Single shot – Indwelling catheter• Local wound infiltration
  61. 61. Multimodal analgesia should consist of…. Combination of Agents• Newer ‘Novel’ Centrally acting I. V. Non-Opioid agents 2-agonists Parenteral Paracetamol NSAIDs, COX-2 selective inhibitors (coxibs) Ketamine , Tramadol, Neostigmine Gabapentin / Pregabalin• Opioids• Local anaesthetics: local anaesthetic block – Local infiltration – Local nerve block – Plexus nerve block – Neuraxial block
  62. 62. Proposed Protocols MMA- I• Pre-medication/ Analgesia with Dexmedetomidine• Dose: 1 µg/ kg I.V. for 10 minutes• Induce with small dose of Propofol• Rocuroneum for Intubation/ Maintenance• Inhalational iso or sevoflurane• Near end of surgery I.V. Paracetamol- 15mg/ kg- upto 1g max.• Continue every 4-6 hourly , till NBM status, switch to oral NSAID/COXIB• Dexmedetomidine infusion: Post operative or ICU sedation/analgesia in ventilated patients: Dex. 0.5 µg/kg/hr infusion
  63. 63. Proposed Protocols MMA- II• Neuraxial Blockade with 0.75% ropivacaine; 3 ml intra-thecal or 12-15 ml epidural• Sedation with Dexmedetomidine : 0.2 to 0.7 µg/kg/hr.• Post-op analgesia with : either epidural LAA with or without adjuvant; like clonidine 75µg, midazolam 0.5 mg, fentanyl 25-50 µg• I V Paracetamol &/ or Dexmedetomidine
  64. 64. Proposed Protocols MMA- IIIPoint Modifications• Addition of clonidine 1 or 1.5 µg/kg to bupi. In peri-bulbar/ Supraclavicular /axillary block• Addition of dexmedetomidine 10 µg (0.5 ml) or fentanyl 0.5 - 1 µg/kg to 3.5 ml Bupivacaine intra-thecally• Addition of clonidine 75µg (0.5ml) to 3 ml bupivacaine intra thecally• Dex : I.V. 1 µg/kg as an Intraop analgesic for day care/ short GA Spont. Respn.
  65. 65. Summarizing• Alpha2 adrenoceptor agonists are very unique class of drugs• imidazole group• latest entrant: Dexmedetomidine• mimics many of the actions of mythical ‘ideal’ sedative/analgesic agent• wide spectrum of actions encompassing the entire peri-operative period and then beyond that, into the critical care services/ as a part of Multi-Modal Analgesia
  66. 66. Conclusion• Dexmedetomidine is revolutionizing, the intra- venous anaesthesia• Changing pre-operative sedation, pre- anaesthetic anxiolytic medication and even the day care procedures like conscious sedation• changing our viewpoint of providing intra and post- operative analgesia, without any potential and significant side-effects of existing agents employed for this purpose.
  67. 67. Conclusion• In critical care setting as a sedative/ analgesic, without much deleterious effects, morbidity and dependence of the patients on the ventilators.• It’s use via various other routes, than; conventional intra-venous route such as neuraxial, regional is taking the drug into New Frontiers• All these indications with an enviable safety profile makes it a very promising, desirable and dependable drug!!
  68. 68. Take Home Message!• Quest for an ‘Ideal’ peri-operative sedative- analgesic goes on… &… on…&….on!!• α2 agonists are unique class of drugs, with many desirable properties!!• Clonidine and now dexmedetomidine, are versatile, multi-faceted and potent drugs!!!• With more evidence, it’s value is more or less clearly established, as sole or as part of MMA!!!!• It is revolutionizing the modern anaesthetic practice!!!!!
  69. 69. Take Home Message! On the basis of available evidence & self experience• No Hesitation in making it a part of my Anaesthetic Practice &• No Hesitation in recommending it, to others to do so!!
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