Cain dex peds board review

DexmedetomidineJames G. Cain, MD, MBA, FAAPJames G. Cain, MD, MBA, FAAP

Past President, International Trauma Anesthesia and Critical Care Society Past President, International Trauma Anesthesia and Critical Care Society Past President, West Virginia State Society of Anesthesiologists Past President, West Virginia State Society of Anesthesiologists

Director, Perioperative Medical Services, Children’s Hospital of Pittsburgh Director, Perioperative Medical Services, Children’s Hospital of Pittsburgh of UPMC of UPMC

Director, Trauma Anesthesiology, Children’s Hospital of Pittsburgh of Director, Trauma Anesthesiology, Children’s Hospital of Pittsburgh of UPMCUPMC

Visiting Associate Professor, University of PittsburghVisiting Associate Professor, University of Pittsburgh

2

DisclosuresDisclosures

Drug Safety Monitoring BoardDrug Safety Monitoring Board HospiraHospira

Off label uses will be discussedOff label uses will be discussed No labeled uses for pediatrics! No labeled uses for pediatrics!

3

Dexmedetomidine Dexmedetomidine Labeling: Pediatric UseLabeling: Pediatric Use

The efficacy, safety, and The efficacy, safety, and pharmacokinetics of Precedex in pharmacokinetics of Precedex in pediatric patients less than 18 years pediatric patients less than 18 years of age have not been established. of age have not been established.

Therefore, Precedex should not be Therefore, Precedex should not be used in this population.used in this population.

4

Dexmedetomidine labeled Dexmedetomidine labeled prescribingprescribing

IndicationsIndications Sedation of initially intubated and mechanically ventilated patients during Sedation of initially intubated and mechanically ventilated patients during

treatment in an intensive care setting. treatment in an intensive care setting. Administer Precedex by continuous infusion not to exceed 24 hours Administer Precedex by continuous infusion not to exceed 24 hours

Sedation of non-intubated patients prior to and/or during surgical and other Sedation of non-intubated patients prior to and/or during surgical and other proceduresprocedures

Dosage and administration Dosage and administration Individualize and titrate Precedex dosing to desired clinical effect. Individualize and titrate Precedex dosing to desired clinical effect.

Administer Precedex using a controlled infusion device. Administer Precedex using a controlled infusion device.

For Intensive Care Unit Sedation: For Intensive Care Unit Sedation: Generally initiate at one mcg/kg over 10 minutes, followed by a maintenance infusion of 0.2 to 0.7 Generally initiate at one mcg/kg over 10 minutes, followed by a maintenance infusion of 0.2 to 0.7

mcg/kg/hr mcg/kg/hr

For Procedural Sedation: For Procedural Sedation:

Generally initiate at one mcg/kg over 10 minutes, followed by a Generally initiate at one mcg/kg over 10 minutes, followed by a maintenance infusion initiated at 0.6 mcg/kg/hr and titrated to achieve maintenance infusion initiated at 0.6 mcg/kg/hr and titrated to achieve desired clinical effect with doses ranging from 0.2 to 1 mcg/kg/hr.desired clinical effect with doses ranging from 0.2 to 1 mcg/kg/hr.

Alternative doses recommended for patients over 65 years of age and Alternative doses recommended for patients over 65 years of age and

awake fiberoptic intubation patientsawake fiberoptic intubation patients. . Precedex [package insert].

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Dexmedetomidine labeled Dexmedetomidine labeled prescribingprescribing

ContraindicationsContraindications NoneNone

Adverse reactions Adverse reactions Incidence greater than 2% Incidence greater than 2% hypotension, bradycardia, and dry mouth hypotension, bradycardia, and dry mouth

Associated with infusions greater than 24 hours Associated with infusions greater than 24 hours ARDS, respiratory ARDS, respiratory failure, and agitationfailure, and agitation

Drug interactionsDrug interactions Anesthetics, sedatives, hypnotics, opioids: Enhancement of Anesthetics, sedatives, hypnotics, opioids: Enhancement of

pharmacodynamic effects. Reduction in dosage of Precedex or the pharmacodynamic effects. Reduction in dosage of Precedex or the concomitant medication may be requiredconcomitant medication may be required

Disease effecting clearanceDisease effecting clearance Clearance is lower in patients with hepatic impairmentClearance is lower in patients with hepatic impairment

Precedex [package insert]. 6

Hypotension, Hypotension, bradycardia, and sinus bradycardia, and sinus

arrestarrest Young, healthy volunteers with high vagal tone or rapid Young, healthy volunteers with high vagal tone or rapid intravenous or bolus administration.intravenous or bolus administration.

Potential to augment bradycardia induced by vagal stimuli Potential to augment bradycardia induced by vagal stimuli IV anticholinergic agents may be consideredIV anticholinergic agents may be considered

Caution in patients with advanced heart block and/or Caution in patients with advanced heart block and/or severe ventricular dysfunction.severe ventricular dysfunction.

Hypotension and/or bradycardia may be expected to be Hypotension and/or bradycardia may be expected to be more pronounced in patients with hypovolemia, diabetes more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension and in elderly patients.mellitus, or chronic hypertension and in elderly patients.

7

Precedex [package insert].

Traumatic Brain InjuryTraumatic Brain InjuryPossible Spine InjuryPossible Spine Injury

16 year old male16 year old male Frequently agitatedFrequently agitated Frequently Frequently

combativecombative Requires intubationRequires intubation Requires sedationRequires sedation Requires neuro Requires neuro

checkschecks Desire cooperative Desire cooperative

patientpatient

Children’s Hospital of Pittsburgh of UPMC

8

What are your concerns? Hemodynamic stabilityHemodynamic stability Existing medications’ limitationsExisting medications’ limitations RespiratoryRespiratory IntubationIntubation ICU ICU NeuroNeuro Agitation/delirium concernsAgitation/delirium concerns Ability to do “wake-up” neuro checksAbility to do “wake-up” neuro checks Rapid examRapid exam NeuroprotectiveNeuroprotective

9

Achieving Optimal Achieving Optimal PatientPatientComfortComfort

AnalgesiaAnalgesia

Anxiolysis

AnxiolysisSedation

Sedation

HypnosisHypnosis

Amnesia

10

The Fine Balance in The Fine Balance in Patient ComfortPatient Comfort

11


AnxietyAgitation

HypertensionTachycardia

Unable to perform taskWound disruption

Patient injury

12


Delayed emergence

Airway obstruction

Hypoventilation

Increased PA pressures

Hypotension

Delayed weaning

Increased cost

13

How would you proceed?

14

ConsiderationsConsiderations

What is tWhat is the underlying process he underlying process requiring treatment? requiring treatment?

How does drug/technique address How does drug/technique address

underlying problem underlying problem

RectifyRectify

IgnoreIgnore

ExacerbateExacerbate

15

Airway managementAirway management

Asleep vs. sedatedAsleep vs. sedated FOB?FOB?

PIV placedPIV placed Standard monitorsStandard monitors MedicationsMedications OOptions?ptions?

16

17

OpioidsOpioids

Fentanyl Morphine

18

Opioids: Clinical EffectsOpioids: Clinical Effects

AnalgesiaAnalgesia11

SedationSedation11

ToleranceTolerance11

Respiratory depressionRespiratory depression11

Withdrawal symptomsWithdrawal symptoms11

HypotensionHypotension11

BradycardiaBradycardia22

ConstipationConstipation11

1. Harvey. Am J Crit Care. 1996;5:11. 2. Wagner, O’Hara. Clin Pharmacokinet. 1997;33:426-453.19

SedationSedationSedationSedation

HypnosiHypnosiss

HypnosiHypnosiss

AnxiolysiAnxiolysiss

AnxiolysiAnxiolysissAmnesiaAmnesiaAmnesiaAmnesia

AnalgesiAnalgesiaa

AnalgesiAnalgesiaa

OpioidsOpioids

20

Benzodiazepines Benzodiazepines

Midazolam( Versed )

21

BenzodiazepinesBenzodiazepines

Advantages• Amnesia1

• Anxiolysis1

• Sedation1

Limitations• Respiratory depression2,4 • Hypotension2

• Lack of analgesia4 • Oversedation/deep

sedation2

• Dependence/tolerance2

• Paradoxic agitation2

• Weaning prolonged2,3

• Polyethylene glycol toxicity31. Pepperman. Care of the Critically Ill. 1989;5:197. 2. Harvey. Am J Crit Care. 1996;5:10, 11.

3. Lerch, Park. Br Med Bull. 1999;55:89, 90. 4. Crippen. Crit Care Clin. 1990;6:380. 22


HypnosiHypnosiss

HypnosiHypnosiss



AnalgesiAnalgesiaa

AnalgesiAnalgesiaa

BenzodiazepinesBenzodiazepines

23

Sedative/Hypnotics: Sedative/Hypnotics: PropofolPropofol

Propofol

24

PropofolPropofol

AdvantagesAdvantages• SedationSedation11

• HypnosisHypnosis11

• AnxiolysisAnxiolysis11

• Muscle relaxationMuscle relaxation11

ICPICP11

Cerebral metabolic Cerebral metabolic raterate11

• Relief of Relief of bronchospasmbronchospasm11

LimitationsLimitations• Respiratory depressionRespiratory depression

(enhanced by opioids)(enhanced by opioids)11

• HypotensionHypotension11

• Decreased contractilityDecreased contractility22

• Lack of analgesiaLack of analgesia33

• HypertriglyceridemiaHypertriglyceridemia11

• Preservative issuesPreservative issues44

• Potential for infection Potential for infection necessitates need for necessitates need for regular changing of regular changing of lineslines55

1. Harvey. Am J Crit Care.1996;5:7-16. 2. Lerch, Park. Br Med Bull. 1999;55:90. 3. Wagner, O’Hara. Clin Pharmacokinet. 1997;33:435. 4. Propofol [package insert]. 5. Prielipp et al. Crit

Care Clin. 1995;11:986. 25

Propofol Infusion Propofol Infusion SyndromeSyndrome

Propofol infusion in the ICUPropofol infusion in the ICU Associated with serious adverse events and death in Associated with serious adverse events and death in

several case reportsseveral case reports1-41-4

Propofol infusion syndrome in adultsPropofol infusion syndrome in adults1-31-3:: Associated with high-dose (>5mg/kg/h Associated with high-dose (>5mg/kg/h 83 83

mcg/kg/min), long-term (>48 h) infusionmcg/kg/min), long-term (>48 h) infusion Clinical features: metabolic acidosis, hyperkalemia, Clinical features: metabolic acidosis, hyperkalemia,

hepatomegaly, lipemia, myocardial failure, hepatomegaly, lipemia, myocardial failure, rhabdomyolysisrhabdomyolysis

Propofol infusion syndrome in childrenPropofol infusion syndrome in children4-64-6:: Published and unpublished reports of fatal propofol Published and unpublished reports of fatal propofol

infusion syndrome in pediatric ICUsinfusion syndrome in pediatric ICUs1. Kang TM. 1. Kang TM. Ann Pharmacother.Ann Pharmacother. 2002;36:1453-1456; 2. Cremer OL. 2002;36:1453-1456; 2. Cremer OL. LancetLancet. 2001;13:117-. 2001;13:117-

118. 118. 3. Stelow EB. 3. Stelow EB. Clin ChemClin Chem. 2000;46:577-581. 4. Parke TJ et al. . 2000;46:577-581. 4. Parke TJ et al. Br Med JBr Med J. 1992;305:613-616. . 1992;305:613-616.

5. Bray RJ. 5. Bray RJ. Paediatric Anaesth.Paediatric Anaesth. 1998;8:491-499. 6. AstraZeneca. Letter to health care 1998;8:491-499. 6. AstraZeneca. Letter to health care providers. providers.

March 26, 2001. 7. Markovitz BP et al. March 26, 2001. 7. Markovitz BP et al. Crit Care MedCrit Care Med. 2000;28:2178-2179.. 2000;28:2178-2179.

26


HypnosiHypnosiss

HypnosiHypnosiss



PropofolPropofol

AnalgesiaAnalgesiaAnalgesiaAnalgesia

27

2 2 Agonists: Chemical Agonists: Chemical StructuresStructures

N

N

H

N

Cl

Cl

Dexmedetomidine

Clonidine

CH3

CH3

N

N

CH3H

28

2 2 AgonistsAgonists

ClonidineClonidine

Selectivity: Selectivity: 22::11 200:1 200:111

tt1/21/2 10 hrs 10 hrs11

PO, patch, epiduralPO, patch, epidural22

AntihypertensiveAntihypertensive11

Analgesic adjunctAnalgesic adjunct11

IV formulation not IV formulation not available in USavailable in US

DexmedetomidineDexmedetomidine

Selectivity: Selectivity: 22::11 1620:11620:133

tt1/21/2 2 hrs 2 hrs33

IntravenousIntravenous33

Sedative-analgesicSedative-analgesic33

Primary sedativePrimary sedative Only IV Only IV 22 available for available for

use in the USuse in the US1. Maze. White paper; 2000. 2. Khan et al. Anaesthesia. 1999;54:150. 3. Kamibayashi, Maze. Anesthesiology. 2000;93:1345-1349.

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Peds dex Peds dex pharmacokineticspharmacokinetics

93% protein binding93% protein binding Near complete hepatic metabolism to inactive Near complete hepatic metabolism to inactive

metabolitesmetabolites 85% glucuronidation85% glucuronidation 15% cytochrome P45015% cytochrome P450

7 min redistribution half life 7 min redistribution half life Volume of distribution is 118 LVolume of distribution is 118 L Clearance 15 ml/kg/minClearance 15 ml/kg/min 2 hour elimination half life2 hour elimination half life

May be doubled in severe liver failureMay be doubled in severe liver failure Urinary excretionUrinary excretion

30

α-2-adrenoreceptors Pre and Post synaptic locations

Central and peripheral nervous system Vascular smooth muscle Heart Other organs

Presynaptic activation reduces norepinephrine release Postsynaptic activation hyperpolarizes neural

membranes Acts as a feedback loop, further reducing norepinephrine

release Activation in locus ceruleus produces hypnotic/anxiolytic action

Analgesic properties at pre-synaptic sites in spinal cord

31

2A

?

?

2A

2C

2A

2A

Anxiolysis

2B

2B

XX

2B

X

Reprinted with permission from Kamibayashi, Maze. Anesthesiology. 2000;93:1346. 32

Mechanism for Mechanism for 22-induced -induced sedation/sedation/

hypnosis in the locus ceruleushypnosis in the locus ceruleus

Ca++

Ca++

Ca++

–

– +

Decrease in influx of Ca++

Decrease in actionpotential due to

hyperpolarization

2A

2AR

Go Gk K+

K+

K+

33

No significant ECG No significant ECG changeschanges

Congenital heart diseaseCongenital heart disease 101 post op patients101 post op patients Pre dexmedetomidine ECGPre dexmedetomidine ECG Post dexmedetomidine ECGPost dexmedetomidine ECG Trend toward lower heart rateTrend toward lower heart rate No other significant ECG changesNo other significant ECG changes

34

Rapid bolus dex Rapid bolus dex Cardiac effectsCardiac effects

Routine cath for 12 post cardiac Routine cath for 12 post cardiac transplant patientstransplant patients

0.25 or 0.5 mcg/kg over 5 sec0.25 or 0.5 mcg/kg over 5 sec Hemodynamics pre-bolus, 1 and 5 minuteHemodynamics pre-bolus, 1 and 5 minute HR & CO decreasedHR & CO decreased SBP, DBP, SBP, sPAP, dPAP, wPAP SBP, DBP, SBP, sPAP, dPAP, wPAP

increasedincreased Only value not at baseline at 5 minutes Only value not at baseline at 5 minutes

was HR with 0.5 mcg/kg boluswas HR with 0.5 mcg/kg bolusJooste, et al. Acute Hemodynamic Changes Following Rapid Intravenous Bolus Dosing of Dexmedetomidine in Pediatric Heart Transplant Patients Undergoing

Routine Cardiac Catheterization, Accepted Anesthesia & Analgesia 2010, Manuscript Number: AA-D-09-01438R4

36

No ventilation effectNo ventilation effect

Minimal change in minute Minimal change in minute ventilation even at high doses ventilation even at high doses

No change in CO2 responseNo change in CO2 response

37

Cardiorespiratory and Cardiorespiratory and NeuralNeural

1. Wagner, O’Hara. Clin Pharmacokinet. 1997;33:434, 436, 440. 2. Bhana et al. Drugs. 2000;59:263. 3. Harvey. Am J Crit Care. 1996;5:10, 11.

––DexmedetomidinDexmedetomidinee22

HaloperidolHaloperidol33

PropofolPropofol11

BenzodiazepinBenzodiazepineses11

OpioidsOpioids11

RespiratioRespirationn

Cerebral Cerebral ProtectioProtectio

nnHRHRBPBPAgentAgent

––

––

——==no effect; no effect; =reduced=reduced; ; =further reduced; =further reduced; =significant reduction; =significant reduction; =increased; =increased; =further increased.=further increased.——==no effect; no effect; =reduced=reduced; ; =further reduced; =further reduced; =significant reduction; =significant reduction; =increased; =increased; =further increased.=further increased.

38

Arousability From Sedation Arousability From Sedation During Dexmedetomidine During Dexmedetomidine

InfusionInfusion

40

60

80

100

BIS

Placebo 0.2 0.6

During cognitive and cold pressor testing

Just prior to cognitive and cold pressor testing

Dexmedetomidine Infusion (µgkg-1hr-1)

Adapted from Hall et al. Anesth Analg. 2000;90:701.39

Arousal and Task Performance Arousal and Task Performance During During

Equi-sedative Doses of Equi-sedative Doses of Benzodiazepine Benzodiazepine

or or 22 Agonist in Humans Agonist in Humans

2AgonistBenzodiazepine

Focused attention

Learning

Working memory

Task performance

Critical flicker fusion test

40

41

Dexmedetomidine for Dexmedetomidine for pediatricspediatrics

Enhances post op T&A comfortEnhances post op T&A comfort11

Enhances post op LTR sedationEnhances post op LTR sedation22

No significant effect on upper airway No significant effect on upper airway morphologymorphology3,43,4

Beats propofol for OSA spontaneous ventilationBeats propofol for OSA spontaneous ventilation55

Well tolerated, predictable hemodynamics with Well tolerated, predictable hemodynamics with bolusbolus66

No effect on ECGNo effect on ECG77

Extensive safety in ICUExtensive safety in ICU IV, nasal, buccal, oralIV, nasal, buccal, oral

42

43

Intranasal dex vs oral Intranasal dex vs oral midaz midaz

44

• Bioavailability• Oral 16%, IN 65%, buccal 82%, IM 104%

• Buccal administration 2-4 mcg/kg ~ 1 hour prior to surgery

Analgesic EffectAnalgesic Effect

Disinhibit A5/A7 Disinhibit A5/A7 noradrenergic noradrenergic pathwayspathways

Activate Peri-Activate Peri-Aqueductal Aqueductal Gray; Activate Gray; Activate noradrenergic noradrenergic pathwayspathways

Descending Descending inhibitory inhibitory pathwayspathways

Decrease emotive Decrease emotive aspectsaspects

Decrease emotive Decrease emotive aspectsaspects

SubcorticalSubcortical

Inhibit firingInhibit firingInhibit firingInhibit firingSecond-order Second-order neuronsneurons

Inhibit release of Inhibit release of SP and glutamateSP and glutamate

Inhibit release of Inhibit release of SP and glutamateSP and glutamate

Primary afferent Primary afferent neuronsneurons

Inhibit Inhibit sympathetic- sympathetic- mediated painmediated pain

Inhibit Inhibit inflammationinflammation

Perihperal Perihperal nociceptorsnociceptors

2 2 AgonistsAgonistsOpioidsOpioids

45

Dexmedetomidine spares Dexmedetomidine spares opioids opioids

1. Data on file, Integrated Summaries of Efficacy and Safety. 2. Martin E, Ramsay G, Mantz J, Sum-Ping STJ. The role of the alpha2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. J Intensive Care Med. 2003;18:29-41.

46

47

Intraop dex vs morphine Intraop dex vs morphine for tonsillectomyfor tonsillectomy

48

49

Effect of dex on caudal Effect of dex on caudal with bupivicainewith bupivicaine

50

Dexmedetomidine and Dexmedetomidine and deliriumdelirium

Perioperative infusion of 0.2 Perioperative infusion of 0.2 μμg/kg/hg/kg/h Decreases incidence and frequency Decreases incidence and frequency

of emergence deliriumof emergence delirium No prolongation in time to extubate No prolongation in time to extubate

or discharge or discharge No prolongation in time to discharge No prolongation in time to discharge

Shukry, Mathisen, et al., Pediatric Anesthesia; 15:12, 1098-1104, 2005Shukry, Mathisen, et al., Pediatric Anesthesia; 15:12, 1098-1104, 2005

51

Sleep DeprivationSleep Deprivation

Average amount of sleepAverage amount of sleep

in the ICU is in the ICU is

1 hour, 51 minutes 1 hour, 51 minutes

per 24 hoursper 24 hours

Aurell, Elmqvist. Br Med J. 1985;290:1031.52

Sleep Deprivation: Sleep Deprivation: Cognitive FunctionCognitive Function

Impaired memoryImpaired memory11

Impaired communication skillsImpaired communication skills22

Impaired decision-makingImpaired decision-making33

Confusional stateConfusional state44

Apathy Apathy DeliriumDelirium

1. Harrison, Horne. Q J Exp Psychol. 2000;53I:271. 2. Harrison, Horne. Sleep. 1997;20:871-877. 3. Harrison, Horne. Organ Behav Hum Decis Proc. 1999;78:128-145.

4. Krachman et al. Chest. 1995;107:1713-1720.53

Restorative Properties of Restorative Properties of SleepSleep

Increased rate of healing Increased rate of healing Promotes anabolismPromotes anabolism

Facilitates growth hormone releaseFacilitates growth hormone release

Counteracts catabolismCounteracts catabolism Inhibits cortisol releaseInhibits cortisol release Inhibits catecholamine releaseInhibits catecholamine release

Adam, Oswald. BMJ. 1984;289:1400-1401. Adam, Oswald. Clin Sci. 1983;65:561-567.Krachman et al. Chest. 1995;107:1715.

54

Effect of Sedative AgentsEffect of Sedative Agentson “Repair” Mechanismson “Repair” Mechanisms

2 Agonists

Growthhormone

Cortisol

Catecholamines

Proteinsynthesis

PropofolBenzodiazepines

55

How Closely Do SedativeHow Closely Do SedativeAgents Mimic Nature?Agents Mimic Nature?

2 AgonistsPropofolBenzodiazepines

Tissue repair

Immunefunction

Neuralsubstrates

OppositeOpposite SameSame

OppositeOpposite SameSame

DifferentDifferent SameSame

OppositeOpposite

UnknownUnknown

56

No rebound with No rebound with dexmedetomidinedexmedetomidine

136 patients at 10 institutions136 patients at 10 institutions 1/3 of patients received > 24 hours 1/3 of patients received > 24 hours

of dexof dex Ave 54 hoursAve 54 hours Range 24.5-123.5 hourRange 24.5-123.5 hour

Dasta, et al. Ann Pharmaco 38; 1130-5; 2004

Choosing Choosing the Right Drugthe Right Drug

58

Drug CombinationsDrug Combinations

59

Decreased dose of both drugsDecreased dose of both drugs Decreased incidence of toleranceDecreased incidence of tolerance Decreased individual side effectsDecreased individual side effects Increased risk of combined side Increased risk of combined side

effectseffects Respiratory depressionRespiratory depression HypotensionHypotension

Drug CoadministrationDrug Coadministration

60


HypnosiHypnosiss

HypnosiHypnosiss AnxiolysisAnxiolysisAmnesiaAmnesia

Patient ComfortPatient ComfortPatient ComfortPatient Comfort

AnalgesiaAnalgesia

61

Fentanyl + Midazolam or Propofol

AnalgesiaAmnesia

AnxiolysisHypnosis

Common Opioid + Common Opioid + Sedative CombinationSedative Combination

62

Where Dexmedetomidine Where Dexmedetomidine FitsFits

63

HypnosiHypnosiss

HypnosiHypnosiss



2 Agonists2 Agonists

SedatioSedationn

SedatioSedationn AnalgesiAnalgesi

aaAnalgesiAnalgesi

aa

64

SedatioSedationn

SedatioSedationn

AnalgesiAnalgesiaa

AnalgesiAnalgesiaa

DexmedetomidineDexmedetomidine Primary

Midazolam AdjunctSedation

65

SedatioSedationn

SedatioSedationn

AnalgesiAnalgesiaa

AnalgesiAnalgesiaa


Propofol AdjunctSedation

66

SedatioSedationn

SedatioSedationn

AnalgesiAnalgesiaa

AnalgesiAnalgesiaa

FentanylFentanyl AdjunctAnalgesia


67

SedatioSedationn

SedatioSedationn

AnalgesiAnalgesiaa

AnalgesiAnalgesiaa

MorphineMorphine AdjunctAnalgesia


68

Dexmedetomidine for Dexmedetomidine for airway anesthesiologyairway anesthesiology

Critical airway with local anesthetic Critical airway with local anesthetic allergyallergy11

Difficult airway due to odontogenic Difficult airway due to odontogenic infectionsinfections22

Awake trachAwake trach33

Anterior mediastinal massAnterior mediastinal mass44

No respiratory depressionNo respiratory depression55

69

Dexmedetomidine Dexmedetomidine sedation for our TBI sedation for our TBI

patientpatient Can be used as primary agentCan be used as primary agent Cooperative sedationCooperative sedation Titrate to effectTitrate to effect Blunt hyperadrenergic responseBlunt hyperadrenergic response Dex 0.5mcg/kg/Dex 0.5mcg/kg/hour hour

May require up to 2 mcg/kg/hourMay require up to 2 mcg/kg/hour Narcotic supplemented prnNarcotic supplemented prn

70

Dexmedetomidine Dexmedetomidine sedation sedation

Initiation of dexmedetomidineInitiation of dexmedetomidine Loading dose: when appropriateLoading dose: when appropriate Gradual step-up in dose based on heart rateGradual step-up in dose based on heart rate Titrate to sedation scaleTitrate to sedation scale

Lower doses (<0.7 mcg/kg/hr)Lower doses (<0.7 mcg/kg/hr) Adequate for non-CNS injuryAdequate for non-CNS injury

Higher doses (<2.0 mcg/kg/hr)Higher doses (<2.0 mcg/kg/hr) Agitation associated with CNS injury Agitation associated with CNS injury Withdrawal from alcohol or other drugsWithdrawal from alcohol or other drugs

71

Dexmedetomidine Dexmedetomidine Infusion StrategyInfusion Strategy

Assess volume status of patientAssess volume status of patient

Dex loading dose: 1 mcg/k/hour infusion for 10 minutesDex loading dose: 1 mcg/k/hour infusion for 10 minutes

HypovolemicHypovolemic

Consider adjunct medications?

Consider adjunct medications?

Consider increaseConsider increase

Assess effectAssess effect

Monitor BP/HRthroughout

If bradycardia, consideratropine

Monitor BP/HRthroughout

If bradycardia, consideratropine

Dex continuous infusion: 0.5 to 1.5 mcg/kg/hrDex continuous infusion: 0.5 to 1.5 mcg/kg/hr

Volume preloadVolume preload

EuvolemicEuvolemic

Dex=dexmedetomidine.

InadequateInadequate AdequateAdequate

72

22 Agonists: Agonists:PharmacodynamicsPharmacodynamics

Sedation/hypnosisSedation/hypnosis11

AnxiolysisAnxiolysis11

AnalgesiaAnalgesia11

Sympatholysis (decrease BP, HR, NE)Sympatholysis (decrease BP, HR, NE)11

Reduces shiveringReduces shivering22

Neuroprotective effectsNeuroprotective effects33 No effect on ICPNo effect on ICP33 No effect on SSEPNo effect on SSEP No respiratory depressionNo respiratory depression11

1. Aantaa et al. Drugs of the Future. 1993;18:49-56. 2. Kamibayashi, Maze. Anesthesiology.2000;93:1348. 3. Maze. White paper; 2000.

73

74

Thank youThank you

75

Pittsburgh, Pennsylvania, USA

Health & Medicine

Cain dex peds board review