THE USE OF ANALGESICS, SEDATIVE MEDICATIONS PAIN, SEDATION IN CHILDREN Compiled by Tina M. Slusher, MD University of Minnesota Contributions from: JOHN.

THE USE OF ANALGESICS, THE USE OF ANALGESICS, SEDATIVE MEDICATIONS PAIN, SEDATIVE MEDICATIONS PAIN,

SEDATION IN CHILDRENSEDATION IN CHILDREN

Compiled by Tina M. Slusher, MDCompiled by Tina M. Slusher, MDUniversity of MinnesotaUniversity of Minnesota

Contributions from:Contributions from:JOHN BERKENBOSH, M.D.JOHN BERKENBOSH, M.D.University of LouisvilleUniversity of LouisvilleCHERI LANDERS, M.D.CHERI LANDERS, M.D.University of KentuckyUniversity of KentuckyLYNNE W. COULE, M.D.LYNNE W. COULE, M.D.

Medical College of GeorgiaMedical College of GeorgiaDAVID ROSEN, M.D.DAVID ROSEN, M.D.

West Virginia UniversityWest Virginia University STEVE BARNES, M.D.STEVE BARNES, M.D.

Rush UniversityRush University

• Add oxycotin• Add rectal morphine• Scheduled versus prn

Conflict of Interest

• I have nothing to disclose

Children especially neonates feel less pain than adults w/similar painful stimuli

1. True2. False

Anesthesia Myths cont.

• Wrong!! Children do feel pain and neonates likely feel even more pain

• Pain transmission begins @2weeks gestation w/development of skin and mouth sensory neurons

• Appearance of pain inhibitory apparatus begins at about 32 wks gestation

• <20 years ago common belief was than infants did not feel pain and no anesthesia was used even during surgery

• In 1992, a trial2 showed deep anesthesia during cardiac surgery↓ physiologic stress responses and mortality & gave convincing evidence of importance of adequate analgesia for newborn infants

• Untreated pain may have undesirable long-term consequences, even after fairly minor procedures

NelsonNelson’’s textbooks textbook

Analgesia/Sedation MythsConcerns about respiratory depression make

pain control impossible in childrenWrong again!!!

– Need to titrate and Need to monitor– Easy to overshoot in < 6 months– Caveat in the < 6 month old infant

• Opioids can cause apnea prior to pain relief• Neonates may not get good pain relief from morphine

but is commonly used in neonates-more studies needed.

Concerns about addiction should limit appropriate pain

control

1. True2. False

Analgesia/Sedation Myths

• True addiction rarely happens with appropriate pain control

• “Addiction”– Addiction vs. Tolerance vs.

Dependance

Addiction• A common fear voiced by health care

workers• Includes a psychological “need” or

craving along with physical withdrawal symptoms if medication is discontinued

• People in real pain DON’T become addicted as long as medication titrated to pain

Tolerance• The same dose of medication no longer has

the same effect as when first started• More commonly occurs in patients on long

term continuous infusions of sedatives or analgesics rather than intermittent dosing especially if not titrated to the clinical situation

• There are currently NO medications to which tolerance will not develop

Dependence

• Removing medication results in withdrawal symptoms

• To avoid withdrawal, may need to wean sedative or analgesic or change to long acting agents such as methadone or clonidine when patient has been on the medication for 1 week or more

ASSESSING PAIN• JCAHO – pain as 5th vital sign

(mandate)• Developmental and cultural

barriers– Ability to verbalize– Cultural attitudes to pain

coping/treatment• Non-painful contributors to “pain-

like” behaviors

VAS-can be used in VAS-can be used in 8yo8yoFaces scale Faces scale 4yo 4yo

Assessing Pain cont.• Autonomic measures

– Heart rate– Blood pressure

• Behavioral or combined behavioral-physiologic scales (e.g. facial expression, limb movement ± heart rate & blood pressure

What is Analgesia?

“Relief of the perception of pain without intentional production of a sedated state. Altered mental status may be a secondary effect of medications administered for this purpose.”

MANAGING PAIN• 1990 – WHO pain management ladder

– Stepwise approach, based on anticipated severity

– 1° developed for cancer pain, adapted for all acute pain• Outpatient and inpatient applications

• Enteral and intravenous routes encouraged

WHO LADDERMILD PAIN:

– NSAIDS, Acetaminophen ± adjuvants

MODERATE PAIN:– NSAID or acetaminophen ± weak opioid

(oxy, hydro, codeine) ± adjuvants– IV opioids with scheduled NSAID or acetamin

• PCA vs CI vs intermittent

– Regional Anesthetic techniques

SEVERE PAIN:– IV opioids (PCA/CI) ± adjuvants– Regional Anesthetic techniques ± adjuvants

ANALGESIANSAIDS

• Ibuprofen:– Onset – 60-90 min– Peak – 2-4 hrs– Duration – 6-8 hrs– 80% oral bioavailability– Hepatic metabolism via oxidation,

excreted in urine

ANALGESIANSAIDS

• Ketorolac– 0.5-1 mg/kg q6h, po/IV/IM– Onset – 10/30 min, peak – 40-60/90-

180 min– Duration – ~6 hrs– Similar kinetics in infants, children,

adolescents– Time limited regimen

ANALGESIANSAIDS

• Ketorolac– 0.9 mg/kg equipotent to 0.1 mg/kg morphine

• >5 y.o.

– Munro (2002) – morphine PCA ± q6h ketorolacPSF

• 0.2 mg/kg ketorolac• Sustained morphine, diazepam requirements

– Surgical concerns re impaired wound healing– Some of our orthopedic surgeons (KCH) DO NOT

allow in in scoliosis surgery– Limited data in <6 mo

Morphine• Opioid• Advantages

– Analgesia– Less expensive than fentanyl

• Disadvantages– no amnesia, anxiolysis– Histamine release - wheezing, hypotension– Urinary retention– Longer onset than fentanyl

ANALGESIAMORPHINE

• Dose/route– IV/IM - 0.05-0.1mg/kg/dose - onset 2-3 min,

duration 3-4 hr• infusion 0.01-0.04 mg/kg/hr

– po - 0.2-0.5 mg/kg - slow - onset 30-60 minutes

– onset – <5 min/1 hr– Peak – 20 min/1-2 hr– Duration – 3-5 hr

ANALGESIAMORPHINE

• More widely available than fentanyl

• Advantages:-Cheap

• Disadvantages:– pruritus, hypotension, bronchospasm,

sedation, urinary retention

ANALGESIAFENTANYL

• Synthetic opioid, ~ 100X more potent than morphine

• More “hemodynamically friendly” than morphine– 100x more potent than morphine– shorter duration than morphine

•onset in 2-3 min, lasts 30-60 min– less histamine release than morphine

Fentanyl

• Disadvantages:– no amnesia– “Steel chest” or “rigid chest”

phenomenon•more likely with large bolus dose•Treat with reversal of fentanyl or

paralyzation or midazolam

Fentanyl cont.

• Dose/route:– IV - sedation/analgesia - 1-3

mcg/kg/dose - anaesthesia - 5-10 mcg/kg/dose - infusion - 3-5 mcg/kg/hr– Oral - 5-10 mcg/kg

ANALGESIAFENTANYL

• IV/transmucosal– onset – <2 min/5-15 min– Peak – <5 min/20 min– Duration – 30-60 min/1-2 hr– Transmucosal – 25% buccal (rapid), 75%

GI (slow)

Tramadol• Non-opioid analgesia• Central inhibition of seroton and non-

epinephrine• Causes some inhibition of ascending

pain pathway• PO• Dose 1-2 mg/kg/dose q 4-6 hours (max

400mg/day)

Pethidine• Bad choice but sometimes only

one available• Agonist-Antagonist• Metabolite can build up and cause

respiratory depression w/out adequate pain control

• Often underdosed• Dose 0.3-1mg/kg/dose q6hours

Ketamine

• Low dose ketamine may be alternative for pain control

• See latter section on ketamine for more information

Sucrose/Breastfeeding in Neonates

• Sucrose with or without a pacifier can be used for both pain and stress control in the neonate

• Breastfeeding + sucrose or glucose may be best alternative?

• However, recent article in Lancet questions whether oral sucrose actually does reduce pain because although pain score was lower there was no difference in nociceptive or spinal withdrawal activity (Slater R et al, Lancet. 2010;376:1225-1232

ANALGESIANALAXONE (NARCAN)

• Reverses sedation, analgesia, respiratory depression• NO agonist activity so NO risk sedation/respiratory

depression with overdoses• Dose: 0.1 mg/kg IV/IM

– use incremental doses (0.005-0.01 mg/kg) to avoid adverse

• Adverse:– short half-life, resedation/depression– opioid withdrawal (infants of addicted mothers)– agitation, seizures, N+V

Tina M. Slusher, MDAssociate Professor of Pediatrics

SEDATIONRATIONALE

• Anxiety– underlying illness– separation from parents– transport environment and transfers

• Ability to perform procedure– Safety - risks of motion (invasive)– Motion interference (i.e. radiologic)

PRESEDATION ASSESSMENTHISTORY

• Brief and Targeted:– Procedure being done and why– Pertinent past history

• underlying medical conditions• prior sedations/anaesthetics and reactions to them• Underlying airway issues

– Present medications - consider possible interactions

– Allergies - get specifics - not all reactions are allergies-include food allergies as well

– Family history of anaesthetic reactions– NPO Status– Determine specific sources of anxiety

• Patient’s NPO status– <6 mo 2 hours for clears and 4 hours

for breast milk and 6 hours for formula or food

– >6 mo 2 hours for clears and 6 hours for food unless diabetic or GER or other situations at increased risk for delayed emptying

PRESEDATION ASSESSMENTPHYSICAL EXAM

• Complete vitals, including room air SaO2

• Airway - micrognathia/macroglossia, tonsils/adenoids• obesity (compliance)

• Underlying lung disease - need to pretreat wheezing etc.

• Evidence of hypovolemia• Neurologic status - relates to ability to protect airway

• many of these patients are on other CNS-altering medications

Precautions Include• Airway

– Critical Airway: trauma, anatomic abnormality, neonate, full stomach, loose tooth

• Ventilation– Risk for hypoventilation neonate,

debilitated, mentally compromised patient, hx of apnea

SEDATION EFFECTSCARDIOVASCULAR CONSIDERATIONS

• Primary concern is hypotension– vasodilation (esp. venous) (most agents)

• beware of patient with hypovolemia (presedation fasting)• drugs may be synergistic

– myocardial suppression (barbiturates, propofol)

• Precipitation of dysrhythmias– include contribution of relative bradycardia as

some drugs (opioids) blunt the normal compensatory HR response to vasodilation/hypovolemia

Volume Depletion/Hypotension

(Hemodynamic issues)

• IF intravascularly volume depleted or hypotensive may have a in BP if administered sedatives

• IF intravascularly volume depleted or hypotensive should be appropriately fluid resuscitated & hemodynamically stable PRIOR to receiving sedation!

AGENT DETERMINATION• Relative need for anxiolysis vs analgesia• Depth of sedation desired/required• Duration of procedure• Degree of patient/family anxiety

– prior experiences with procedures sedation

• Underlying medical conditions– include family history of reactions to

anaesthetics– airway - obstruction, oral anatomy, CLDz– hemodynamic - volume status, cardiac function

Sedation and Pain Control are

synonymous.50%50%

1. True2. False

Some drugs like barbiturates actually increase pain by

inhibiting neural pathways

SEDATIONDEFINTIONSMild (Conscious) Sedation

• minimally depressed level of consciousness• ability to independently maintain airway patency

retained• respond appropriately to physical or verbal stimulation

Deep (Unconscious) Sedation• controlled state of decreased or lost consciousness• risk of partial/complete loss of airway protection/patency• partial/complete inability to respond appropriately

General Anaesthesia• medically controlled state of unconsciousness• complete loss of airway protection and responsiveness

Continuum of Consciousness

Awake, baseline

Generalanesthesia

Drowsy

Conscioussedation

Deepsedation

ALL SEDATION CAN PROGRESS TODEEP SEDATION REGARDLESS OF THE DRUG OR DOSE EMPLOYED!

Equipment• Check your equipment & make sure it’s the

right size for your patient and in working condition

• Must have equipment for– Securing airway– Assisting ventilation– Supporting circulation– Suctioning equipment/supplies

• PPV (ambu) bag, appropriate mask, IV supplies, & suctioning equipment are the basic minimum

What is the Best Monitoring Tool

• 1. Pulse oximeter• 2. Blood pressure• 3. Cardiac monitor• 4. Eyeballs

MONITORING

• Absolute MINIMUM:– (after Two eyeballs looking at the patient)

– Continuous HR, SaO2

– Intermittent (q5-15 min) BP

– DOCUMENTATION – frequent HR, RR, BP, SaO2

• Consider:– EKG

– ET-CO2

• Hypercarbia and hypoxemia not always simultaneous

CONCEPTSAnalgesia

Sedation

Anxiolysis

Paralysis

DRUG CLASSES• Sedatives benzodiazepines

barbiturateschloral hydrate2 receptor agonists

• Analgesics opioidsketamine

• Anaesthetics ketaminepropofol

Benzodiazepines

• Amnesia– Antegrade and retrograde

• Anxiolysis• Respiratory Depression• Skeletal muscle relaxation

Midazolam (Versed)

• Advantages:– anxiolysis, sedation, some motion

control– retrograde amnesia– PO, IV, IM, IN, PR dosing routes– onset 2-6 min after IV administration,

45-60 min duration– available reversal agent

• Flumazenil

Midazolam (Versed)• Disadvantages

– No analgesia– Paradoxical reactions– More than additive risk of respiratory

compromise when added to opiate– Neonates: bradycardia, hypotension and

seizures with rapid injection– Peak serum level increased with

itraconazole, erythromycin and clarithromycin

Diazepam• Advantages: Similar to other benzo’s

except longer acting, metabolites can accumulate over time causing toxicity especially w/larger doses

• Dosage for sedation:– 0.04-0.2mg/kg/dose IV/IM q2-4 hours

(maximum 8 mg in 24 hours) – 0.12-0.8 mg/kg/24 hours PO divided q6hours

Barbiturates

• General CNS depressants• Induction of anesthesia• Hypnosis• Sedation• Respiratory depression

Pentobarbital (Nembutal)

• Advantages:– Fairly safe– Sedation, motion control, anxiolysis– Short onset (3-5 min. given IV) and

duration (15-45 min.)– Alternative to chloral hydrate in older

children– PO, IV, IM, PR dosing routes

• longer time to onset and longer duration with routes other than IV

Pentobarbital

• Disadvantages– Enhances pain perception– No reversal agent

Chloral Hydrate• Advantages

– PO, PR dosing• initial 25-100 mg/kg• repeat after 30 min if need 25-50 mg/kg

– Anxiolysis, sedation, motion control– Single dose toxicity is low– Successful in younger patients (< 2-3 yrs)– Many practitioners familiar with its use– Just as good as bourbon

Chloral Hydrate• Disadvantages

– 15-30 min to onset, lasts 1-2 hours– Less successful in older children– High doses can cause respiratory

depression and dysrhythmias– No pain control– Not reversible– Repetitive doses cause metabolites to

accumulate with unknown toxicities

Propofol

• Sedative/hypnotic anesthetic• Increased popularity for procedural

sedation– Rapid onset and recovery– Lack of agitation– Anti-emetic properties

• Deep sedation for short procedures– Consider concomitant analgesic or local

anaesthetic

NO significant Analgesic Properties

PROPOFOL• Administration:

– 1-2 mg/kg/dose – slowly and titrate– Infusion (3-5 mg/kg/hr) or frequent small boluses

• Onset/Duration:– Rapid onset (1-2 minutes)– Rapid recovery - baseline in 10-15 minutes

• Adverse:– Respiratory depression/airway protection

• Dose-dependent• Smaller therapeutic window than ketamine

– Hypotension/bradycardia– Pain at injection site – lidocaine helps~I mix

1mg/kg in first 10cc syringe of propofol ~less problematic w/larger IV’s

Propofol cont.

• Adverse:– Respiratory depression/airway

protection• Dose-dependent• Smaller therapeutic window than

ketamine

– Hypotension/bradycardia– Pain at injection site - lidocaine

Narcotics Plus Benzo’s

• Monitor closely for respiratory depression esp. when used in combination w/benzodiazepines!

• Remember that narcotics plus benzo’s =

more respiratory depression than either alone!

Ketamine• Dissociative anesthetic• Advantages

– provides both analgesia and amnesia– less alteration of upper airway tone and reflexes than benzo’s or narcotics– preserves upper airway tone and reflexes– causes bronchodilatation

• Although studies don’t all agree ketamine likely reduces the dose of morphine when used together. (Carstensen & Moller, BMJ, 2010, 401-6)

Ketamine• Disadvantages

– increases intracranial pressure– laryngospasm– hypersecretory response (can lessen

with use of glycopyrrolate-best or atropine)– emergence phenomenon/agitation

(can lessen with benzo’s)

Ketamine• Relative contraindications

– head injury– airway abnormalities– procedures where posterior pharynx

will be stimulated– glaucoma, acute globe injury– psychosis– thyroid disorder– uncontrolled hypertension

KETAMINE• Dose:

– IV - 1-2 mg/kg initially repeat 0.5-1 mg/kg as needed

– IM - 3-6 mg/kg– PO – 5-10 mg/kg– Suggest adding antisialagogue,

benzodiazepine

Ketamine cont

• Onset/Duration:– rapid onset (<1 min IV, 5-10 minutes

IM, 10-15 PO)– dissociation lasts 15-30 minutes,

return to baseline usually by 30-60 minutes after last dose