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

Conflict of Interest

• I have nothing to disclose

Which of the following is true regarding pain management?

• 1. Pain management affects wound healing

• 2. PTSD is not related to acute pain management

• 3. Neonates don’t feel pain

Importance of Effective Pain Control

• Untreated pain has psychological effects

• Exacerbates injury and may mortality

• Contributes to delayed wound healing

• Contributes to development of chronic pain and PTSD

Bowman et al J of Trauma &Acute Care Surgery 2011

Non-pharmacological pain control-audiovisual

distraction

• Decreased pain• Increased cooperation• Decreased time of procedure

Swiss Med Wkly. 2008 Oct 4;138(39-40):579-84.The efficacy of non-pharmacological methods of pain management in school-age children receiving venepuncture in a paediatric department: a randomized controlled trial of audiovisual distraction and routine psychological intervention.Wang ZX, Sun LH, Chen AP.

J Prev Med Hyg. 2012 Mar;53(1):44-8.Distraction techniques in children during venipuncture: an Italian experience.Bagnasco A, Pezzi E, Rosa F, Fornonil L, Sasso L.

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 trial 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.

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

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.”

WHO Golden Rules of Pain Management

1. By the Clock– Regular scheduling ensures steady

blood level– PRN results in cycles of pain often

leading to increased pain med needs

2. With the child– Regular pain assessment using

appropriate scales

• Scales available on line, standard textbooks or hospital.

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

8-10mg/kg/dose q 6-8hr PO or PR

NSAIDS cont.

• Naproxen ≥12yo to ≤65yo 200mg q6-8hr

• Diclofenac-start in adult 50mg tid • All NSAIDS have similar analgesic

properties if used in equi-analgesic dose and many of the same side effects

ANALGESIA NSAIDS cont. Ketorolac

– Only use IV if patient unable to take po NSAID– At equianalgesic dosing no more effective than

ibuprofen but has greater side effects– 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

Codeine• Poor analgesic properties• Genetic variation means may lead

to toxic levels i.e ultra-rapid metabolism can result in toxic accumulation of morphine

• Don’t use if at all possible

Oxycodone• Management of moderate-severe

pain• Comes as immediate and

sustained release

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

Rectal Morphine also option0.2 mg/kg/dose

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– IN-1.5-2.0 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 but works on opioid

receptors w/weak opioid• Don’t mix w/strong opoid like morphine or pain

make worsen• 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• Use has decreased as a reversal agent because of risk of

re-sedation• 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

Naloxone in Low Doses

• Used to treat itching associated w/narcotics as low-dose continuous infusion

• Used to Rx nausea unresponsive to anti-emetics

• Can be given po to treat constipation from narcotics unresponsive to other bowel regimes [(1mg/mL) 4 mL po BID to TID in older children/adults; 1-2mL po BID-TID in younger children]

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

• Vital signs including baseline SaO2

• General evaluation looking for evidence – illnesses, toxicity– volume depletion– obesity

• Airway exam – micrognathia/macroglossia, tonsils/adenoids– ability to open mouth well

• Lung exam– Wheezing, air exchange

• Cardiac exam – Unrecognized heart disease– Volume status

• Neurologic status– Ability to protect airway– Ability to cooperate with exam.

ASA Physical Status

Class I: Healthy patientClass II: Systemic disease-well controlledClass III: Severe systemic diseaseClass IV: Severe systemic disease that is

a constant threat to lifeClass V: Moribund / not expected to

survive without surgery

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 and if available ET-CO2 probably better than sat

• as it picks up changes quicker

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 *For IN ideally needConcentrated 5mg/mL

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

Increases pain perception

Thiopental

• Primarily used for induction of anesthesia, seizure control and increased ICP

• Provides no pain control

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

DEXMEDETOMIDINE• Sedation, anxiolysis

• Analgesia – some but not great

• Hypertension

• Bradycardia/hypotension

• Diuresis

• Minimal respiratory depression

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– IN-9mg/kg– Suggest adding antisialagogue,

benzodiazepineTsze IN Ketamine for procedural sedationIn pediatric laceration repair : a preliminary reportPediatr Emerg Care 2012

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