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SEDATION and ANALGESIA SEDATION and ANALGESIA in the PICUin the PICU
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GOALSGOALS
• Analgesia for painful diseases and Analgesia for painful diseases and proceduresprocedures
• Compliance with controlled Compliance with controlled ventilation and routine intensive ventilation and routine intensive carecare
• Amnesia for the periods of sedationAmnesia for the periods of sedation• Reduce the physiological responses Reduce the physiological responses
to stressto stress• Avoid complicationAvoid complication
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SEDATION and ANALGESIASEDATION and ANALGESIA
• Inadequate analgesia and Inadequate analgesia and postsurgical stress response is a postsurgical stress response is a metabolic, humoral, and metabolic, humoral, and hemodynamic response following hemodynamic response following injury or surgeryinjury or surgery
• This neuroendocrine cascade leads to This neuroendocrine cascade leads to increased oxygen consumption, increased oxygen consumption, increased carbon dioxide production, increased carbon dioxide production, and a generalized catabolic state and a generalized catabolic state with a negative nitrogen balancewith a negative nitrogen balance
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SEDATION/ANALGESIASEDATION/ANALGESIASedation (sedaSedation (seda//shun) [L. shun) [L. sedatio, sedatio, to calm, to calm,
allay]. The act of calming, especially by allay]. The act of calming, especially by the administration of a sedative, or the the administration of a sedative, or the state of being calm.state of being calm.
Analgesia (an-al-jeAnalgesia (an-al-je//zi-ah) [G. insensibility, zi-ah) [G. insensibility, from from anan - privative,negative + - privative,negative + algesis,algesis, sensation of pain] A condition in which sensation of pain] A condition in which nocioceptive stimuli are perceived but are nocioceptive stimuli are perceived but are not interpreted as pain; usually not interpreted as pain; usually accompanied by sedation without loss of accompanied by sedation without loss of consciousness.consciousness.
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IDEAL PICU IDEAL PICU SEDATIVE/ANALGESIASEDATIVE/ANALGESIA
• Rapid onsetRapid onset• Predictable durationPredictable duration• No active metabolitesNo active metabolites• Rapid recoveryRapid recovery• Multiple routes of deliveryMultiple routes of delivery• Easy to titrateEasy to titrate• Minimal cardiopulmonary effectsMinimal cardiopulmonary effects• Not altered by renal or hepatic diseaseNot altered by renal or hepatic disease• No drug interactionsNo drug interactions• Wide therapeutic indexWide therapeutic index
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COMMON DRUGS UTILIZEDCOMMON DRUGS UTILIZED
• Opiates (Narcotics)Opiates (Narcotics)• BenzodiazepinesBenzodiazepines• Chloral hydrateChloral hydrate• BarbituratesBarbiturates• KetamineKetamine• PropofolPropofol• NeurolepticsNeuroleptics• ParalyticsParalytics
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SITUATIONS REQUIRING SITUATIONS REQUIRING SEDATIVES/ANALGESIASEDATIVES/ANALGESIA
• MECHANICAL VENTILATIONMECHANICAL VENTILATION– Respiratory failureRespiratory failure– AirwayAirway– NeurologicalNeurological
• POST OPERATIVEPOST OPERATIVE• HEAD INJURYHEAD INJURY• PULMONARY HYPERTENSIONPULMONARY HYPERTENSION• PROCEDURESPROCEDURES
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OPIOIDSOPIOIDS• First line drugsFirst line drugs• Provide analgesia and sedation, NOT Provide analgesia and sedation, NOT
amnesiaamnesia• Act similarly as a classAct similarly as a class• Produce delayed gastric emptying, Produce delayed gastric emptying,
decreased intestinal peristalsis, and decreased intestinal peristalsis, and urinary retentionurinary retention
• Narcotic to be used:Narcotic to be used:– MorphineMorphine– FentanylFentanyl– MethadoneMethadone
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OPIOIDSOPIOIDSROUTE OF ADMINISTRATIONROUTE OF ADMINISTRATION– IVIV– OralOral– TransmucosalTransmucosal– TransdermalTransdermalMODE OF ADMINISTRATIONMODE OF ADMINISTRATION– Intermittent/on demand (as necessary)Intermittent/on demand (as necessary)– Fixed intervalFixed interval– Continuous infusionContinuous infusion– PCAPCA
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MORPHINEMORPHINE• Gold standardGold standard• Hepatic metabolismHepatic metabolism• Depresses respiration by altering Depresses respiration by altering
chemoreceptor sensitivity to COchemoreceptor sensitivity to CO22
• Depresses rate over tidal volumeDepresses rate over tidal volume• Decreases sigh frequency Decreases sigh frequency • Can cause hypotension due to Can cause hypotension due to
histamine mediated vasodilationhistamine mediated vasodilation• Can block compensatory Can block compensatory
catecholamine effectcatecholamine effect• Prolonged clearance in neonatesProlonged clearance in neonates
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MORPHINEMORPHINE
• IV intermittentIV intermittent– 0.1 mg/kg q 3 - 0.1 mg/kg q 3 -
4 hrs4 hrs• IV continuousIV continuous
– 0.05 mg - 0.1 0.05 mg - 0.1 mg/kg/hrmg/kg/hr
• PO scheduledPO scheduled– 0.3 mg/kg q 3 - 0.3 mg/kg q 3 -
4 hrs4 hrs
• PCA dosingPCA dosing– Initial dosing: 50 Initial dosing: 50
mcg/kg q 10 mcg/kg q 10 minutes until minutes until comfortablecomfortable
– Demand dose: 20 Demand dose: 20 - 40 mcg/kg- 40 mcg/kg
– Lock-out period: Lock-out period: 10 minutes10 minutes
– 4-hour limit: 0.25 4-hour limit: 0.25 mg/kgmg/kg
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FENTANYLFENTANYL• Synthetic opiate, 100 x more potent than Synthetic opiate, 100 x more potent than
morphinemorphine• Rapid onset, highly lipophilic, rapidly Rapid onset, highly lipophilic, rapidly
crosses BBB, redistributed to fatty tissuecrosses BBB, redistributed to fatty tissue
• Short distribution tShort distribution t1/21/2, long elimination , long elimination tt1/21/2
• Minimal hemodynamic effectMinimal hemodynamic effect• Blunts pulmonary vascular responsesBlunts pulmonary vascular responses• May produce “chest wall rigidity”, May produce “chest wall rigidity”,
reversed with relaxants or naloxonereversed with relaxants or naloxone
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FENTANYLFENTANYL• IV intermittent dosingIV intermittent dosing
– 1-2 mcg/kg q 1-2 hrs1-2 mcg/kg q 1-2 hrs• IV continuous dosingIV continuous dosing
– 1-2 mcg/kg/hr1-2 mcg/kg/hr• Transdermal delivery system availableTransdermal delivery system available
– Not recommended in children less Not recommended in children less than 12 yrsthan 12 yrs
– 25,50,75,100 mcg/hr25,50,75,100 mcg/hr– 25 mcg/hr is equivalent to 15 mg 25 mcg/hr is equivalent to 15 mg
morphine in a 24 hr periodmorphine in a 24 hr period
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METHADONEMETHADONE• Equipotent to morphineEquipotent to morphine• Minimal hemodynamic effectsMinimal hemodynamic effects• Long half lifeLong half life• Sedation and euphoric properties less Sedation and euphoric properties less
pronounced than morphine pronounced than morphine • Useful for pain control and abstinence PO Useful for pain control and abstinence PO
dosingdosing– 0.1 mg/kg q 4-8 hrs0.1 mg/kg q 4-8 hrs– 50 % oral bioavailability50 % oral bioavailability– Drug accumulation with repeated doses Drug accumulation with repeated doses
caused by extensive protein bindingcaused by extensive protein binding
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MODE OF ADMINISTRATIONMODE OF ADMINISTRATION
• Intravenous bolus administrationIntravenous bolus administration– CommonCommon– PRN - as neededPRN - as needed– Half-life of drug determines Half-life of drug determines
intervalinterval– Disadvantage of pain Disadvantage of pain
breakthroughbreakthrough
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IV BOLUS ADMINISTRATIONIV BOLUS ADMINISTRATION
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CONTINUOUS INFUSIONCONTINUOUS INFUSION• Utilized when prolonged analgesia Utilized when prolonged analgesia
and sedation neededand sedation needed• Less labor intensiveLess labor intensive• Better analgesia, initial bolus Better analgesia, initial bolus
importantimportant• Need for dedicated IV siteNeed for dedicated IV site
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CONTINUOUS INFUSIONCONTINUOUS INFUSION
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PCAPCA• Patient controlled analgesiaPatient controlled analgesia• Allows patient to administer a preset Allows patient to administer a preset
amount of narcotic at preselected amount of narcotic at preselected intervalsintervals
• Improved analgesia with decreased Improved analgesia with decreased narcotic usenarcotic use
• Option to include low basal rateOption to include low basal rate• Nurse controlled analgesiaNurse controlled analgesia
– Eliminates delayEliminates delay– Allows delivery via a closed systemAllows delivery via a closed system
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PCAPCA
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OPIATE SIDE EFFECTSOPIATE SIDE EFFECTS
• RESPIRATORY DEPRESSIONRESPIRATORY DEPRESSION– Reversal - Nalaxone (Narcan)Reversal - Nalaxone (Narcan)
• Full reversal 0.1 mg/kgFull reversal 0.1 mg/kg•Partial reversal - titrate to effectPartial reversal - titrate to effect•Half life is less than narcoticsHalf life is less than narcotics• IV,IM,Sub Q, ETTIV,IM,Sub Q, ETT•Abrupt reversal may result in Abrupt reversal may result in
nausea, vomiting, sweating, nausea, vomiting, sweating, tachycardia, increased BP, and tachycardia, increased BP, and tremorstremors
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OPIATE SIDE EFFECTSOPIATE SIDE EFFECTS• Pruritis Pruritis
– Individual variability and susceptibility, Individual variability and susceptibility, alleviated by Benadrylalleviated by Benadryl
• Tolerance Tolerance – Need for increase in dose to achieve Need for increase in dose to achieve
the same effectthe same effect– Generally develops after 2-3 days of Generally develops after 2-3 days of
frequent/continuous usefrequent/continuous use– Greater with fentanylGreater with fentanyl– Treated by increasing the dose as Treated by increasing the dose as
neededneeded
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OPIATE SIDE EFFECTSOPIATE SIDE EFFECTS• DEPENDENCEDEPENDENCE
– Physiological state leading to abstinence Physiological state leading to abstinence syndrome on withdrawal of the drugsyndrome on withdrawal of the drug
– Generally develops after 7-10 days of Generally develops after 7-10 days of sustained usesustained use
– Symptoms include: mydriasis, Symptoms include: mydriasis, tachycardia, goose bumps, muscle jerks, tachycardia, goose bumps, muscle jerks, vomiting, diarrhea, seizures, fever, vomiting, diarrhea, seizures, fever, hypertensionhypertension
– Treated with gradual withdrawal of the Treated with gradual withdrawal of the drugdrug
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OPIATE SIDE EFFECTSOPIATE SIDE EFFECTS• DEPENDENCEDEPENDENCE
– In general the longer the period of treatment In general the longer the period of treatment the longer the period of withdrawal neededthe longer the period of withdrawal needed
– A child is at risk for dependence if they have A child is at risk for dependence if they have been on narcotics for a weekbeen on narcotics for a week
– Finnegan scoring to monitor adequate Finnegan scoring to monitor adequate weaning doseweaning dose
– Weaning strategies can vary, typically 10% Weaning strategies can vary, typically 10% decrease per daydecrease per day• Do not spread the dosing interval beyond Do not spread the dosing interval beyond
the normal dosing interval, rather decrease the normal dosing interval, rather decrease the dosethe dose
• Can substitute methadone and wean q 48 Can substitute methadone and wean q 48 hrs over a longer time periodhrs over a longer time period
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BENZODIAZEPINESBENZODIAZEPINES• First line agents for sedationFirst line agents for sedation• Provide hypnosis, anxiolysis, Provide hypnosis, anxiolysis,
antegrade amnesia, and antegrade amnesia, and anticonvulsant activityanticonvulsant activity
• NO ANALGESIANO ANALGESIA• Can cause abstinence syndrome after Can cause abstinence syndrome after
prolonged useprolonged use• Mechanism in the limbic system via Mechanism in the limbic system via
the inhibitory neurotransmitter, the inhibitory neurotransmitter, gamma aminobutyric acid (GABA)gamma aminobutyric acid (GABA)
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DIAZEPAM (VALIUM)DIAZEPAM (VALIUM)• Sedating, variable amnesia, anxiolyticSedating, variable amnesia, anxiolytic• Irritating to veins, pain in PIVIrritating to veins, pain in PIV• Multiple active metabolites Multiple active metabolites
– Advantage for prolonged sedationAdvantage for prolonged sedation– Disadvantage for rapid arousalDisadvantage for rapid arousal– Not recommended for continuous Not recommended for continuous
infusioninfusion• Half-life 12-24 hrsHalf-life 12-24 hrs• Hepatic metabolismHepatic metabolism
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LORAZEPAM (ATIVAN)LORAZEPAM (ATIVAN)• Improved amnesiaImproved amnesia• No active metabolitesNo active metabolites• Half life 4-12 hoursHalf life 4-12 hours• Metabolized by glucuronyl Metabolized by glucuronyl
transferasetransferase– Less influence from other drugsLess influence from other drugs– Better preserved in patients with Better preserved in patients with
liver diseaseliver disease
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MIDAZOLAM (VERSED)MIDAZOLAM (VERSED)• Rapid onsetRapid onset• Rapid metabolismRapid metabolism• Good amnesiaGood amnesia• Water soluble, no Water soluble, no
pain with injectionpain with injection• Half life 2 -4 hoursHalf life 2 -4 hours• Hepatic metabolism Hepatic metabolism
with renal excretionwith renal excretion– Active hydroxy-Active hydroxy-
metabolite may metabolite may accumulateaccumulate
• Other routes of Other routes of administrationadministration– OralOral– NasalNasal– RectalRectal– Sublingual Sublingual
• Less absorption Less absorption requiring increase requiring increase dosingdosing
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MIDAZOLAMMIDAZOLAM• Reports of dystonia and Reports of dystonia and
choreoathetosis post infusion, choreoathetosis post infusion, greater risk in neonatesgreater risk in neonates
• Heparin decreases protein binding, Heparin decreases protein binding, increases free drugincreases free drug
• Disadvantage cost Disadvantage cost – 20 kg patient20 kg patient– 80 $/day compared to Ativan = 30 80 $/day compared to Ativan = 30
$/day$/day
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BENZODIAZEPINES BENZODIAZEPINES SIDE EFFECTSSIDE EFFECTS
• RESPIRATORY DEPRESSIONRESPIRATORY DEPRESSION– Less than narcotics, but potentiated Less than narcotics, but potentiated
with narcoticswith narcotics– Dose relatedDose related– ReversalReversal
• Flumazenil - benzodiazepine receptor Flumazenil - benzodiazepine receptor antagonistantagonist
•Contraindicated in patients with Contraindicated in patients with chronic benzo use for seizures, mixed chronic benzo use for seizures, mixed overdose, TCA’s - may result in overdose, TCA’s - may result in seizuresseizures
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BENZODIAZEPINESBENZODIAZEPINESSIDE EFFECTSSIDE EFFECTS
• Choreoathetoid movement disorderChoreoathetoid movement disorder• Tolerance Tolerance
– As with narcotics may need to increase As with narcotics may need to increase dose following 2-3 days usedose following 2-3 days use
• DependenceDependence– Withdrawal carefully and slowly if on Withdrawal carefully and slowly if on
greater than 7-10 daysgreater than 7-10 days– Signs of withdrawal - tremor, Signs of withdrawal - tremor,
tachycardia, hypertension, tachycardia, hypertension, – Rapid withdrawal may promote Rapid withdrawal may promote
seizuresseizures
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CHLORAL HYDRATECHLORAL HYDRATE• Sedative hypnotic agent Sedative hypnotic agent • Metabolized in the liver to its active form, Metabolized in the liver to its active form,
trichlorethanoltrichlorethanol• Half life 8-12 hoursHalf life 8-12 hours• Oral or rectal administrationOral or rectal administration• Onset of action delayedOnset of action delayed• Paradoxical reaction in some older childrenParadoxical reaction in some older children• Not to exceed 100 mg/kg/day - i.e.: Not to exceed 100 mg/kg/day - i.e.:
25mg/kg/q 6 hrs25mg/kg/q 6 hrs• Caution in children < 3 months or with Caution in children < 3 months or with
hepatic dysfunctionhepatic dysfunction
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BARBITURATESBARBITURATES• SedativeSedative• Respiratory depression dose Respiratory depression dose
dependentdependent• Negative inotropic effects/vasodilation Negative inotropic effects/vasodilation
- decreased cardiac output- decreased cardiac output
• Decreased cerebral ODecreased cerebral O2 2 consumptionconsumption– CBFCBF– ICPICP
• AnticonvulsantAnticonvulsant
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BARBITURATESBARBITURATES
• Useful in patients with increased Useful in patients with increased ICPICP
• Short acting barbiturate useful Short acting barbiturate useful for sedation for for sedation for procedure/imaging in procedure/imaging in hemodynamically stable childhemodynamically stable child
• Alkaline solution, often Alkaline solution, often incompatible with TPN or meds.incompatible with TPN or meds.
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MAJOR TRANQUILIZERSMAJOR TRANQUILIZERS
• PhenothiazinePhenothiazine– ThorazineThorazine
• ButyrophenonesButyrophenones– DroperidolDroperidol– HaloperidolHaloperidol
• Common in adult ICU, uncommon in PICUCommon in adult ICU, uncommon in PICU• Side effects hypotension due to alpha Side effects hypotension due to alpha
blockade and extrapyramidal effectsblockade and extrapyramidal effects• At times useful in the difficult to sedate At times useful in the difficult to sedate
childchild
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KETAMINEKETAMINE• Dissociative IV anestheticDissociative IV anesthetic• Good amnesia and somatic analgesiaGood amnesia and somatic analgesia• Anesthetic state classically described as Anesthetic state classically described as
a functional and electrophysiological a functional and electrophysiological dissociation between the dissociation between the thalamoneocortical and limbic systemthalamoneocortical and limbic system
• Chemically related to phencyclidine and Chemically related to phencyclidine and cyclohexaminecyclohexamine
• Water and lipid solubleWater and lipid soluble• Quickly crosses blood-brain barrier, < 30 Quickly crosses blood-brain barrier, < 30
secondsseconds
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KETAMINEKETAMINE• Redistribution half-life 4.7 minutesRedistribution half-life 4.7 minutes• Elimination half-life 2.2 hoursElimination half-life 2.2 hours• Clinical effects evident within one minute, Clinical effects evident within one minute,
resolution within 15 - 20 minutes of doseresolution within 15 - 20 minutes of dose• BronchodilationBronchodilation• Sialagogue -“promoting the flow of saliva”Sialagogue -“promoting the flow of saliva”
– Administer with an anticholinergicAdminister with an anticholinergic•Atropine or RobinolAtropine or Robinol
• Minimal net hemodynamic effectMinimal net hemodynamic effect– Negative inotropeNegative inotrope– Central effect - Central effect - HR, HR, SVRSVR
• Good choice in shock or status asthmaticusGood choice in shock or status asthmaticus
UTHSCSA
UTHSCSA
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KETAMINEKETAMINE• Risk of laryngospasmRisk of laryngospasm• Risk of emesis/aspirationRisk of emesis/aspiration• Increases ICP , globe pressureIncreases ICP , globe pressure• Seizure inducingSeizure inducing• Emergent reactions, hallucinationsEmergent reactions, hallucinations
– Improved with administration of a benzodiazepineImproved with administration of a benzodiazepine• IM: IM: 2 - 4 mg/kg dose q 30 minutes - 1 hour2 - 4 mg/kg dose q 30 minutes - 1 hour• IVIV
– Intermittent dosingIntermittent dosing• 1 -2 mg/kg dose q 30 minutes to 1 hr1 -2 mg/kg dose q 30 minutes to 1 hr
– Continuous dosingContinuous dosing• 1 - 3 mg/kg/hr1 - 3 mg/kg/hr
UTHSCSA
UTHSCSA
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PROPOFOLPROPOFOL
• Sedative/hypnoticSedative/hypnotic– Dose dependent - conscious sedation Dose dependent - conscious sedation
to general anesthesiato general anesthesia– Rapid onset (20-50 seconds)Rapid onset (20-50 seconds)– Quick recovery ( within 30 minutes of Quick recovery ( within 30 minutes of
d/c)d/c)– Lack of active metabolitesLack of active metabolites– Metabolized in liverMetabolized in liver– Excreted in urineExcreted in urine
UTHSCSA
UTHSCSA
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PROPOFOLPROPOFOL• Lipid emulsion, reports of anaphylaxisLipid emulsion, reports of anaphylaxis
– Soybean oil, egg lecithin, and Soybean oil, egg lecithin, and glycerolglycerol
• Decreased ICP, may lower CPP Decreased ICP, may lower CPP • Decreased sympathetic toneDecreased sympathetic tone
– Contraindicated in hemodynamically Contraindicated in hemodynamically unstableunstable
– Moderate respiratory depressionModerate respiratory depression• Pain with injection/infusion sitePain with injection/infusion site
– Improved with use of 1% lidocaineImproved with use of 1% lidocaine– 0.5 mg/kg0.5 mg/kg
UTHSCSA
UTHSCSA
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PROPOFOLPROPOFOL• Neurologic sequelaNeurologic sequela
– Opisthotonic posturingOpisthotonic posturing– Myoclonic movementsMyoclonic movements
• Metabolic acidosis reported with use > 24 hrsMetabolic acidosis reported with use > 24 hrs• Contraindicated for long term use Contraindicated for long term use • DosesDoses
– 1 - 3 mg/kg induction1 - 3 mg/kg induction– 20 - 100 mcg/kg/min20 - 100 mcg/kg/min– Increase infusion rate 5-10 mcg/kg/min Increase infusion rate 5-10 mcg/kg/min
increments of 5 - 10 minutesincrements of 5 - 10 minutes