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 ?

Dr. Mridul M. Panditrao

CONSULTANTDEPARTMENT OF ANESTHESIOLOGY AND

INTENSIVE CARE

PUBLIC HOSPITAL AUTHORITY’S RAND MEMORIAL HOSPITAL

GRAND BAHAMA,THE BAHAMAS

• FORMERLY:PROFESSOR & HEAD

In-charge SURGICAL ICUDEAN OF THE MEDICAL FACULTY

Department of Anaesthesiology &Critical Care

D. Y. patil medical collegePimpri, Pune, Inida

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 transmitters or neuromodulators influencing them

• adrenergic receptors : on the basis of effective potency of different naturally occurring or synthetic catecholamines.

Adrenergic Receptors

• Alpha (α) A

& B

• Beta (β)

alpha1

alpha2

beta1

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

Adrenergic Receptors : alpha 2

• pre• post & • Extra synaptic sites of sympathetic terminals

Only the pre-synaptic type of alpha2 receptors are of clinical importance

Drew GM, Whiting SB. Evidence for two distinct types of post synaptic alpha adrenoceptors in vascular smooth muscle in vivo. Br J Pharmacol. 1979; 67: 207-215


• 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

http://www.baylorhealth.com/


• 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 expressed

in 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

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


Clonidine

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.

Parenteral Clonidine

• Intravenous: obtundation of pressor response

• As an adjuvant to LAAs : Neuraxially: intra-thecally as well as

epidurally Supraclavicular Block Peribulbar Block

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


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

application in humans• Structure:

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

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

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 spinal cord dorsal horn. Brain res.1985; 309: 177- 182

CELLULAR MECHANISM

Ca++

Ca++

Ca++

–

– +

Decrease in influx of Ca++

Decrease in actionpotential due to

hyperpolarization

a2A

a2AR

Go Gk K+

K+

K+

CNS ACTIONS

Dexmedetomidine

• 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 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

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

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

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

http://www.baylorhealth.com/

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.

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


• 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.com

Aanta R, Jaakola ML, Kallio A, Kanto J. Reduction of minimum alveolar concentration of isoflurane by dexmedetomidine .Anesthesiology 1997;80 : 1055-1060

http://dexmedtomidine.com/


• 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


• 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 saline Scheinin B, Lindgren L, Bandel T, Scheinin H, Scheinin M. Dexmedomidine attenuates sympatho

adrenal responses to tracheal intubation and reduces need for thiopentone and peri-operative fentanyl Br J Anaesth 1992; 68: 126-131

Menda F, Koner O, Sayin M, Ture H et al. Dexmedetomidine as an adjunct to anaesthetic induction to attenuate hemodynamic response to endotracheal intubation in patients undergoing fast track CABG. Ann Can J Anaesth 2010’ 13: 16-21


• 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 J Cereb 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-femoral bypass graft: a case report. AANA Journal2005; 73:357-360

alpha 2 Adrenergic Receptor Antagonist

Atipamezole• Effectively reverses Psychomotor

side-effects• Reverses Sedation &

Sympatholysis• Reverses Analgesia• t ½ is 1 ½ - 2 hours.

To compare the efficacy of

Dexmedetomidine vs

Fentanyl

as sedative & analgesic in

short general anaesthesia in

day care obstetric &

gynaecological surgeries

AIMS AND OBJECTIVES

• To compare the time required for onset and offset of sedation, quality of intra-operative & post-operative analgesia and the time required for post-operative recovery using Inj. Dexmedetomidine and Inj. Fentanyl

• To evaluate cardio-respiratory and any other systemic side effects at equi-sedative doses

METHODOLOGY

• Age group 18 - 65 years of ASA-I & II •Randomized into two equal groups of ten each by computer 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

• 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 evaluated periodically for

- vitals - sedation using Ramsay sedation scale

- visual analog scale - time of rescue analgesia (when VAS >5) - Standard Aldrete score for post anaesthesia

recovery

METHODOLOGY

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

0

10

20

30

40

50

60

70

80

90

On table AFT PMD AFT IND At 5 min At 10 min At 15 min At end Post - op

PR

Avera

ge

Group A

Group B

P < 0.05 after premedication.

RESULTS

• No significant change in blood pressure seen in Dex. group whereas continuous fluctuation of systolic BP seen in fent.group

• No significant change in diastolic BP & Respiratory rate seen in any of the groups

• significant fall in saturation was observed with Fentanyl group

• The time of eye opening is highly significantly early in Dex. group (p<0.001) and delayed eye opening seen with fentanyl group

Line diagram showing comparision of systolic blood pressure in study groups

90

95

100

105

110

115

120

125


SBP (mm Hg)

Ave

rag

e

Group A

Group B

Line diagram showing comparision of SPO2 in study groups

0

10

20

30

40

50

60

70

80

90

100

110


SPO2

Ave

rag

e Group A

Group B

0

1

2

3

4

5

6

7

Av

era

ge

Eye opening after surgery (min)

Bar chart showing comparison of eye opening after surgery in study group

Group A

Group B

RESULTS

• The post operative analgesia duration was more in Dex. group (approx. 4-6 hrs.), whereas in Fentanyl group patients required rescue analgesia within 1 – 1.5 hrs of surgery

• The sedation was highly significantly profound in fentanyl group according to Ramsay sedation score (p < 0.001) after 15 min of surgery

• The quality of recovery was highly significantly better (Aldrete score = 9+)was observed in most of the patients after 30 min in Dex.group & Similar results were seen only after 1.5 – 2 hrs. in Fentanyl Group

Line diagram showing comparision of VAS score in study groups

0

2

4

6

8

At End of surgery At 30 min At 1 hr At 1.5 hr At 2 hr

VAS Score

Ave

rag

e

Group A

Group B

Line diagram showing comparision of Ramsay sedation in post operative in study groups

0

1

2

3

4

End of surgery At 15 min At 30 min At 1 hr At 2 hr

Ramsay sedation

Ave

rag

e

Group A

Group B

P < 0.001 at 1.5 hrs.

P < 0.001 at 15 min.Line diagram showing comparision of standard aldrete score in post operative in study

groups

0

2

4

6

8

10

12

End of surgery At 15 min At 30 min At 1 hr At 1.5 hr At 2 hr

Standard aldrete score

Ave

rag

e

Group A

Group B

P < 0.001 at 15,30, 60 min.

TO EVALUATE THE EFFECT OF ADDITION OF DEXMEDETOMIDINE 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 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

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

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

• No statistically significant difference for age, height , weight, Sex wise and ASA distribution in both groups

RESULTS

• Difference in sensory onset not statistically significant

• Motor onset significantly shorter in Dexmedetomidine Group (t value-2.54,

p value < 0.05) • Difference in peak

sensory insignificant

• Peak motor significantly longer in Dex Group(t value-4.59, p value<0.0001)

RESULTS

0

1

2

3

4

5

6

7

8

Av

era

ge

Time of Peak sensory (T3) Time of Peak motor(T4)

After spinal anesthesia

Multiple bar diagram showing comparison of time of sensory and motor Peak after spinal anesthesia in study groups

Group A

Group B

• 2 segment sensory regression

• motor regression and

• time of rescue analgesia significantly longer in Dex. Group

RESULTS Parameters Group A Group B t

ValueP

ValueMean SD (n=20)

Mean SD (n=20)

2 segment sensory regression (T5)

190.3 34.80 98.65 14.95

10.81 <0.0001

Motor regression (T6)

265.05 57.50 138.7 14.76

9.51 <0.0001

Time of rescue analgesia (T7)

342.75 76.94 189 20.71 8.62 <0.0001

0

50

100

150

200

250

300

350

Ave

rag

e

2 segment sensoryregression (T5)

Motor regression(T6)

Time of rescueanalgesia (vas > 7)

(T7)

Level of sensory blockade

Multiple bar diagram showing comparison of level of sensory blockade in study groups

Group A

Group B

• Both groups with manageable Bradycardia & Hypotension0

1

2

3

4

No

. o

f cases

Bradycardia Hypotension

Side effect

Multiple bar diagram showing side effect wise distribution of cases in study groups

Group A

Group B

Line diagram showing comparision of heart rate in study groups

0

10

20

30

40

50

60

70

80

90

100

HR (min)

Avera

ge

Group A

Group B

Line diagram showing comparision of systolic blood pressure in study groups

0

20

40

60

80

100

120

140

SBP (mm Hg)

Avera

ge

Group A

Group B

Line diagram showing comparision of diastolic blood pressure in study groups

0

10

20

30

40

50

60

70

80

90

Pre – op At 3 min At 10min

At 15min

At 30min

At 45min

At 60min

End ofSurgery

Post -op

DBP (mm Hg)

Avera

ge

Group A

Group B

To compare the Sedation and Analgesia produced by Dexmedetomidine and

Butorphanol in Critically Ill patients on Mechanical

Ventilation: A Randomized Double Blind Controlled Trial

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.

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

• 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

RESULTS

Time interval between the muscle relaxant doses was nearly double in Dexmedetomidine group, hence the requirement of muscle relaxant was nearly half, suggesting an excellent quality of sedation and analgesia.

Demographically there was no significant difference in the 2 groups.

0

5

10

15

20

25

30

Av

era

ge

Total requirement of M.R (mg)

Bar chart showing comparison of total requirement of M.R in study group

Group A

Group B

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

Avera

ge

Average time interval between M.R dose (min)

Bar chart showing comparison of average time interval between M.R dose in study group

Group A

Group B

RESULTS

0

2

4

6

8

10

12

14

16

18

Av

era

ge

Total No of hrs on ventilator (hr)

Bar chart showing comparison of total no of hrs on ventilator in study group

Group A

Group B

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

Av

era

ge

Sedation score

Bar chart showing comparison of sedation score in study group

Group A

Group B

Patients receiving Butorphanol were drowsier as assessed by Brussels’ sedation score but it was not statistically significant;

Butorphanol group patients needed about 30-60 minutes more to be weaned off from the ventilator

Haemodynamically patients in both A and B groups were stable

RESULTS

0

1

2

3

4

5

6

No

of

ca

se

s

Nausea / vomiting

Bar chart showing comparison of Nausea / vomiting in study group

Group A

Group B

Line diagram showing comparision of respiratory rate in study groups

0

2

4

6

8

10

12

14

16

T0 T1 T2

RR

Ave

rag

e

Group A

Group B

Respiratory rate during weaning and after extubation was significantly low in Butorphanol Group, suggesting some amount of respiratory depression

Few patients in Butorphanol group complained of nausea and vomiting during weaning and after extubation where as there was no such complaints in patients of Dex. group

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

Indications: Future plans

• Use of dexmedetomidine as an adjuvant to Local Anaesthetic Mixture, in peribulbar block

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.

“Real World”: Multimodal Analgesia

• Reduced doses

• Improved pain relief

• Reduce severityof AEs

• Earlier discharge

• Decreased costs

Opioids

Non opioids :α2 agonistsNSAIDs, coxibs,paracetamol,nerve blocks

Potentiation

Kehlet et al. Anesth Analg. 1993;77:1048-1056 (B).

Preventive Multimodal Analgesia

• Significant improvement in

– Pain reduction

– Opioid use

– Opioid-related AEs

– Recovery or day ward length of stay

–Unplanned admission to the hospital

Reuben et al. Acute Pain. 2004;6:87-93.

Multimodal analgesia - methods

• Preemptive analgesia• Analgesics– Single shot– Infusions– PCA

• Nerve blocks– Single shot– Indwelling catheter

• Local wound infiltration

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

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

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

Proposed Protocols MMA- III

Point 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.

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

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.

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!!

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!!!!!

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!!

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

Health & Medicine

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