Pediatric Procedural Sedation Course

Pharmacology

Pharmacology

• Regardless of medication, dose or route of administration, adherence to the pediatric procedural sedation policy is required.

• When choosing drugs for procedural sedation the provider must consider

• Pharmacodynamics • Pharmacokinetics • Dose Response

Pharmacodynamics Pharmacodynamics refers to the action of a drug

• Drugs used for procedural sedation may be divided into two general groups: 1) Those which provide sedation 2) Those which provide primarily analgesia

• Use of drugs that provide analgesia should be determined by whether the procedure is associated with pain or discomfort

• Use of drugs that provide only sedation should be considered for non-painful procedures such as MRI or CT scans

Pharmacokinetics

Pharmacokinetics affects the onset & duration of action of the drug and is affected by the route of administration • Drugs for procedural sedation may be given orally, IV, or

intra-nasally • Providers must be familiar with routes of administration,

dosages, and effects of medications typically used for procedural sedation

• Combinations of medications must be used with caution: increased potency compared to individual medications • IV administration of combinations of medications is

the leading cause of respiratory depression in children undergoing procedural sedation

Pharmacokinetics

Routes of Administration: • Oral medications may have a bitter taste that may

not be tolerated • Consider mixing with flavored syrup to mask the

bitterness • Condition of the nasal mucosa can effect intranasal

absorption • Presence of mucus • Epistaxis • Destruction from surgery • Use of nasal vasoconstrictors

• The advantage of IV administration is the ability to titrate medications to the desired effect

Dose Response Dose response is affected by titration and synergy

• The amount of effect achieved for a given dose of medication is referred to as the dose-response curve for that drug

• Most sedative and analgesic medications have non-linear dose-response curves

• Non-linear curves result in initial doses having little or no effect until a certain point, followed by clear incremental effect for each dose Dose Response Curve

• The ideal manner in which to administer a medication is to titrate that drug to achieve the desired effect.

• An appropriate "loading dose" should be administered followed by smaller doses with adequate time between doses to evaluate effect

• Starting with small doses then escalating the dose due to a lack of initial effect, will lead to overdose during medication titration

Dose Response

Question 1 Which of the following is the most appropriate method

of administering medication to children for procedural sedation:

Administer a loading dose followed by smaller dose allowing adequate time between doses to evaluate effect

Start with a small dose then escalate the dose if you do not see an initial effect

You are correct!

• The ideal manner in which to administer a medication is to titrate that drug to achieve the desired effect.

• An appropriate "loading dose" should be administered followed by smaller doses with adequate time between doses to evaluate effect

• Starting with small doses then escalating the dose due to a lack of initial effect will lead to overdose during medication titration

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• That is not the best choice for administering sedation to children.

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Dose Response Dose Stacking Administration of medications before the peak effect of a previous dose has been reached will result in an excessive total drug effect over time (dose stacking)

Synergy • Combinations of medications are more potent than an

individual medication leading to increase risk of complications

• An example of synergy is the increased risk of respiratory depression when opioids are administered with benzodiazepines

Dose Calculation and Documentation

• Special attention must be paid to the accurate calculation of dosage based on the child’s weight in kilograms

• Documentation on the Sedation/Analgesia Assessment and Procedure Record must include: • Name of medication • Dose and time including duration of administration • Route and site of administration • Patient response including adverse effects

Medications Frequently Used During Procedural Sedation

Fentanyl - analgesia and mild sedation Chloral Hydrate - sedative hypnotic, no analgesia Midazolam - sedation, anxiolysis, amnesia, no analgesia Pentobarbital - sedation, no analgesia Narcan - opioid agonist reversal agent for fentanyl Flumazenil - reversal agent for midazolam Ketamine - restricted use Propofol - restricted use Dexmedetomidine - restricted use

Question 2 Which of the following medications frequently used

for procedural sedation is best known for its anxiolytic and amnesic properties?

chloral hydrate midazolam

naloxone pentobarbital

You are correct!

Midazolam is best know for decreasing anxiety and producing amnesia.

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Mild Analgesia

Sucrose Pacifier: • Pacifier dipped in sugar water or sucrose solution for

infants under 2 months of age provides mild analgesia • Sucrose solution may also be applied underneath tongue

• Consider use in neonates undergoing brief painful procedures such as blood draws and lumbar punctures

• Studies demonstrated decrease in crying time

Does not require strict adherence to pediatric procedural sedation policy

Procedural Sedation

Oral Chloral Hydrate: • Sedative hypnotic with NO analgesic effects • Used for pediatric patients during painless

procedures such as diagnostic radiology • Advantage: lack of associated respiratory

depression when used as a single agent Requires strict adherence to monitoring and

observation requirements of the pediatric procedural sedation policy

Procedural Sedation Oral Chloral Hydrate: • Respiratory depression likely when combined with

opioids or other sedatives • Long half-life can result in prolonged sedation,

especially in infants • requires prolonged observation and monitoring prior to

discharge

• Ensure that children are at pre-sedation baseline prior to discharge • Risk for airway obstruction should the head fall forward while

child is secured in car seat • Respiratory arrests have occurred during transport home for

children in car seats

• Inform parents of potential safety risks associated with prolonged sedative effects

Procedural Sedation

Oral Chloral Hydrate: • Dose: 50 – 75 mg/kg/dose orally (Max 1 g/dose)

May repeat 30 minutes after initial dose to maximum of: 120 mg/kg total or 1 g total for infants and 2 g total for

children • Onset: 10 – 20 minutes • Peak effect: Up to 60 minutes

• Increased in infants • Elimination half-life: 4 – 12 hours • Duration: 4 – 8 hours • Contraindications: GFR < 50

Procedural Sedation Midazolam: • Water soluble benzodiazepine devoid of analgesic

properties • Causes skeletal muscle relaxation, amnesia, and

anxiolysis • Can be used:

• to achieve anxiolysis and cooperation • as a single agent for non-painful procedures • in combination with an analgesic or local

anesthetic for painful procedures

Procedural Sedation Midazolam: • Advantages:

• Short duration • Predictable onset • Lack of active metabolites • Low risk of respiratory depression when used alone • Anterograde and retrograde (less frequent) amnesia

Requires strict adherence to monitoring and observation requirements of the pediatric procedural sedation policy

Procedural Sedation Oral Midazolam: • Dose: 0.25 – 0.5 mg/kg (MAX 20 mg dose)

• Onset: 10 – 20 minutes • Peak effect: 30 minutes • Elimination half-life: 3 – 4.5 hours • Duration: 2 hours

• Availability • Syrup 10mg/5ml

Intranasal Midazolam: • Dose: 0.2 – 0.3 mg/kg (MAX 7 mg initial dose) • Use is limited by:

• Burning upon application to the nasal mucosa • Most children will only accept this route of

administration once • Onset: Within 5 minutes • Peak effect: 10 minutes • Elimination half-life: 2 – 4.5 hours • Duration: 30 – 60 minutes • Availability:

• Use the 5 mg/ml IV concentration

Procedural Sedation

Procedural Sedation

Intravenous Midazolam: • Slow IV administration recommended with close observation

for respiratory depression • Potent sedative effect when combined with intravenous

opioids for painful procedures • Pronounced anterograde amnesia and (at times) retrograde

amnesia with IV administration • Slurred speech coincides with onset of anterograde

amnesia • The value of amnesia and anxiolysis can not be

underestimated in the performance of painful procedures in children

Intravenous Midazolam: • Effects of midazolam may be altered by underlying

medical conditions or medications • Cimetidine, carbamazepine, phenobarbital,

phenytoin, and valproic acid • Children may require higher dose due to altered metabolism

through p450 enzymes

• Heparin • Children may require lower dose due to increase in the

available drug

• Renal failure • Children may require lower dose due to an increase in the

available drug

Procedural Sedation

Intravenous Midazolam: • Dose: 0.05 – 0.1 mg/kg (MAX 2 mg initial dose)

• May repeat 3 – 4 minutes after initial dose to a total dose of 0.2 mg/kg

• A maximum IV dose of 0.05 mg/kg is recommended when combining with narcotics

• Onset: Within 1 – 5 minutes • Peak effect: 5 – 7 minutes • Elimination half-life: 1 - 4 hours • Duration: mean 2 hours

Procedural Sedation

Flumazenil: • Reverses effects of benzodiazepines

• Should be immediately available when using benzodiazepines for sedation

• Dose: 0.01mg/kg (MAX 0.2 mg initial dose) • May be repeated 5 times as needed • Patients > 50 kg – doses up to 1 mg may be used

• Resedation may occur requiring additional flumazenil doses • Monitor children receiving flumazenil for a minimum of one

hour prior to discharge, regardless of Aldrete score

Use of reversal agents is discouraged and must never be used to expedite discharge

Procedural Sedation

Procedural Sedation Fentanyl: • Very potent synthetic opioid, ideal for painful procedures in

children • As a sole agent offers:

• analgesia • mild sedation • short duration of action

• Bradycardia may occur from vagal nerve stimulation • Drug metabolism may be prolonged in neonates and

children with hepatic dysfunction Requires strict adherence to monitoring and observation

requirements of the pediatric procedural sedation policy

Fentanyl: Respiratory depression:

• Significant risk • may outlast opioid effects by 60-90 minutes

• Markedly increased when combined with midazolam or other sedatives; IV access recommended

Chest wall rigidity: • May occur with rapid intravenous fentanyl dosing • If chest wall rigidity occurs:

• call for help immediately • support respirations • be prepared to administer a neuromuscular blocker

Procedural Sedation

Intranasal Fentanyl: • Dose: 2 µg/kg/dose (MAX 50 µg) • Onset: Almost immediate • Peak effect: Maximal analgesic and respiratory

depressant effect occurs in 5 minutes

Procedural Sedation

Intravenous Fentanyl: • Dose: 0.5 – 1 µg/kg/dose (MAX 50 µg)

• May be titrated to a total dose of 4 – 5 µg/kg • Onset: Almost immediate • Peak effect: Maximal analgesic and respiratory

depressant effect occurs within 5 minutes • Elimination half-life:

• Terminal half-life 16 hours

• Duration: 30 – 60 minutes

Procedural Sedation

Naloxone: • Opioid antagonist: reverses opioids’ depressive effects • Administer intravenously, intramuscularly, or intratracheally

• Preferred route of administration is intravenous • Abrupt effect

• Sedated children will often be quite disturbed when awakened by naloxone administration

• Administer by slow titration when possible • Most common side effect: nausea • Unusual catastrophic events (such as sudden death)

described in adults – not reported in children

Procedural Sedation

Naloxone: • Dose for oversedation

• 0.01 mg/kg IV, maximum dose 0.4mg IV • May repeat after 2 minutes for a total of 2 doses

• Dose for respiratory arrest • 0.1 mg/kg, maximum dose 2 mg

• Availability: 0.4 mg/ml

Procedural Sedation

Fentanyl + Midazolam Dosing Recommendation

• Midazolam 0.05 mg/kg IV every 3 minutes to achieve desired level of sedation • Max dose 2 mg • Total maximum dose 0.2 mg/kg

• Fentanyl 1 mcg/kg IV every 5 minutes to achieve desired level of sedation • Max dose 50 mcg • Total maximum dose 5 mcg/kg or total of 5 doses

• Administer each drug separately, allow sufficient time to reach full effect before administering another dose

Question 3

Which medication is used to reverse the effects of benzodiazepines?

naloxone

chloral hydrate flumazenil

fentanyl

You are correct!

• Flumazenil is given to reverse the effects of benzodiazepines and should be immediately available when using benzodiazepines for sedation.

• Resedation may occur requiring additional doses therefore children who receive flumazenil for oversedation/respiratory depression should be monitored for a minimum of one hour prior to discharge, regardless of Aldrete score

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Procedural Sedation Pentobarbital: • Oxybarbiturate • Used for nonpainful procedures requiring immobility • Effectiveness enhanced when combined with midazolam • Respiratory depression can occur

• ~5% rate of oxygen desaturation • Excitatory phase can occur prior to sedative effect • Agitation can occur during recovery

• Occurs more frequently when children are aroused before the sedative effects wear off

Requires strict adherence to monitoring and observation requirements of the pediatric procedural sedation policy

Procedural Sedation Pentobarbital: • Dose: 2 mg/kg IV (MAX 50mg)

• May repeat at 1 mg/kg IV every 3 minutes to achieve desired level of sedation

• May be titrated to a total dose of 7 mg/kg or 200 mg

• Onset: within 1-3 minutes • Elimination half-life: 25 hours +/- 16 hours • Duration: 15 minutes per drug insert, but clinical

effects last 30-90 minutes when titrated

Question 5 Which of the following medications provide

analgesia and sedation?

chloral hydrate

fentanyl

midazolam

pentobarbital

You are correct!

Fentanyl provides both analgesia and a mild sedative effect

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That medication does not produce both analgesia and sedation.

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Medications for Restricted Use Medications listed here are restricted to administration by

the following providers: Ketamine

• ICU physicians, Anesthesiologists, Emergency physicians

Propofol • ICU physicians, Anesthesiologists, Emergency physicians • Separate LMS training and credentialing is required

Dexmedetomidine • ICU physicians, Anesthesiologists, Emergency physicians,

and nurses with Pediatric PSC Service • Separate LMS training and credentialing is required

Ketamine: • Derivative of PCP • Binds to opioid receptors providing intense

analgesic, sedative, and amnestic effects • Useful in painful procedures

• Demonstrated to be safe for children • Spontaneous respirations and airway reflexes are

maintained • Eyes remain open with a slow nystagmic gaze, intact

corneal and light reflexes

Procedural Sedation

Ketamine: • Causes increases in heart rate, blood pressure, cardiac

output, and intracranial pressure • Slowly redistributes into the peripheral tissues (average

15 minutes) • Decrease in CNS levels correlate with return of

coherence • Refer to nursing policy Management of the Pediatric

Patient Receiving Ketamine-NURS 0519 for additional information

Procedural Sedation

Dexmedetomidine: • Alpha 2 agonist • Provides sedation and anxiolysis via receptors in the locus

ceruleus • Provides analgesia via receptors in spinal cord • Decreases stress response • No significant respiratory depression

• Enhanced effect when administered with anesthetics, sedatives, hypnotics and opioids

• May require reduced doses when combined with other agents

• Please refer to nursing policy Management of the Patient Receiving Dexmedetomidine for Non-Painful Procedural Sedation for additional information

Procedural Sedation

Procedural Sedation

Propofol: • Ultra short-acting sedative-hypnotic agent • Causes global depression of the central nervous

system by binding to a different ץ-aminobutyric acid (GABA) receptor site than benzodiazepines

• Some amnestic and anti-emetic effects • NO analgesic effect • Used for induction and maintenance of general

anesthesia • Can only be administered by an attending physician • Please refer to the Pediatric Sedation Policy for Non-

Anesthesiologists – ADMIN 0160, appendix D for additional information

Question 6

Registered nurses who have successfully completed all procedural sedation credentialing requirements may administer ketamine or propofol to children

undergoing procedural sedation

true

false

You are correct!

• While nurses may administer ketamine under the direction of a credentialed attending physician, administration of propofol is restricted to attending physicians only.

• An attending physician must be present at the patient’s bedside throughout the sedation and is responsible for the sedation, not the procedure.

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You have successfully completed the Pharmacology module.

Congratulations!

Pediatric Procedural Sedation Course